Genes Referenced here (New genes
will be linked from this page) See also Alzgene
GWAS from Genome.gov
Very Large scale (N >10,000) ABCA7
APOE
BIN1
CD2AP
CD33
CLU
CR1
EPHA1
MS4A4A
MS4A4E MS4A6A PICALM
TREM2
(HLA-DRB5
HLA-DRB1
SORL1
SLC24A4
PTK2B
ZCWPW1
CELF1
FERMT2
CASS4
INPP5D
MEF2C
NME8)
Other GWAS APOC1
CUGBP2
DISC1
FAM113B
FRMD4A
FRMD6
GAB2
HPCAL1 MTHFD1L PAX2 PCDH11X PVRL2 RFC3 SASH1 TOMM40
TTLL7 VSNL1 ZNF224 PPP1R3B
(CDKAL1
OSBPL6 PTPRG PDCL3)
- Cholesterol/lipid CETP
CH25H
CYP46A1
DHCR24
DCHS2
FDPS
HMGCR
HMGCS2
LIPA
LIPC
LPL
NPC1
NPC2
SOAT1
SREBF1
- Lipoprotein A2M
ABCA1
ABCA2
ABCA7
ABCC2
ABCG1
ACAD8
APOA1
APOA4
APOA5
APOC1
APOC2
APOC3
APOC4
APOD
APOE
LDLR
LPA LRP1 LRP1B LRP2 LRP6 LRP8 LRPAP1 NR1H2 OLR1 PPARA PPARG SORL1 VLDLR
- APP processing APBA1
APBB1
APBB2
APBB3
APH1A
APH1B
APP BACE1
BACE2
NCSTN
PSEN1
PSEN2
PSENEN
- Growth factors and related BDNF
EPHA1
FGF1
IGF1
NRG3
NTRK1
NTRK2
PIK3R1 VEGF
- Complement
CFH
CLU
CR1
C4A
C4B
- Chemokines and cytokines CCL2
CCL3
CCR2
IL10
IL18
IL1A
IL1B
IL1RN
IL33
IL6
IL8
TGFB1
TNF
- Glutathione/oxidative
stress GPX1
GSTM1
GSTM3
GSTO1
GSTP1
GSTT1
HMOX1
MPO
NFE2L2
NOS1
NOS2
NOS3
NQO1
SOD2
- Homocysteine/methionine
BLMH
CBS
MTHFD1L
MTHFR
MTR
MTRR PON1
PON2
- Mitochondria
ATP5H
ATP6 ATP7B
ATP8 ATP8A1 COX1 COX2 COX3 COX10 COX15 CYTB MT-COI MT-DLOOP MT-haplo
MT-L2 MT-RNR1 ND1
ND2
ND3 ND4 ND4L ND5 ND6
TFAM
TOMM40
- Immune CD2AP
CD33
CD36
CD86 CRP EBF3 FCER1G HLA-A2 HLA-DRB1 MICA TAP2
TLR2
TLR4
TLR9
- Androgen/Oestrogen AR
CYP19A1
ESR1
ESR2
HSD11B1
FSHR
HSD17B10
- Ubiquitin UBD UBE2I UBQLN1 UCHL1
- Channels CACNB2
CALHM1
KCNH7
KCNJ6
KCDT12 KCNU1
SCN2A
- Cholinergic BCHE
CHAT
CHRFAM7A
CHRNA3
CHRNA4
CHRNA7
CHRNB2
- Glutamate GRIN2B
GRIN3A
- Monoamine ADRB1
ADRB2
COMT
DBH
HTR6
HTR7
MAOA
SLC6A4
- Heat shock DNAJC28 HSPA1B
HSPA5
- Retinoid ALB
LRAT
RXRA
TTR
- Structural COL11A1 COL25A1
DNM2
DNMBP
EXOC4
KNS2
MAPT
MYH13 MYH8
- Viral
EIF2AK2 PVRL2
- Adhesion ACAN
BCAM DCHS2
HSPG2
ICAM1
NCAM2
- Metabolic ALDH18A1
ALDH2
DLD
DLST
GAPDH
GAPDHS
- ACE
ADAM12
ADAM9
ADAM10
AGBL4 AGER
AGT
AGPAT1
AHSG
ANGPT4
ANK3
ARID1B
ARSA
ARSB
ATF7
ATXN1
BAT1
BCR
BIN1
C9ORF72
CALHM1
CAND1
CARD8
CAV1
CCNT1 CD14
CDC2
CDK5
CDK5R1
CDKN1A
CDKN2BAS CELF2
CECR2 CHD4 CLOCK
CLSTN2 CNTN5 CSF1 CSK CST3 CTNAA3 CTNNA3 CTNND2 CTSD
CTSS CUBN CWC15 DAB1
DAPK1 DEFB122 DFNB31 DISC1
DKK1 DOPEY2 DPYSL2 DSC1 DYRK1A
ECE1
EFNA5
ELAVL4 ENTPD7 F13A1 FAS
FTO
GAB2
GALP
GBP2 GNA11 GNB3 GOLM1
GOLPH2
GRHL
GRN GSK3B HBG2 hCG2039140 HFE
HHEX
HNT
HTRA2
IDE
IREB2
KCTD2
KIF18B KLF5 LCK
LHCGR LMNA LPAR5 LRRK2 LRRTM3
LSM14A MAGI2 MAL2 MAPK8IP1
MC2R MCM3AP MCPH1 MEF2A MEFV MME MMEL2 MMNAT3 MMP1 MMP3
MPHOSPH1
MSRA MS4A4E MS4A6A NAT2 NCAPD2 NEDD9 NGB NINJ2
NLRP1
NMNAT3 NP NPAS2 NPFFR2 NR3A ODZ3 OGG1 OPCML SIGMAR1
OTC PARP1 PAX2 PCDH11X PCGF5 PCK1 PCMTD1 PDE9A PDLIM5 PGBD1 PICALM
PIN1
PKP2P1 PLA2G3 PLAT
PLAU
PLTP PNMT POMT1 PON2 PON3 POU2F1 PPM1H PPP1R11 PPP1R3A PPP2R2B PPPR31
PRND PRNP PRSS7 PRUNE2 PTGS2 PTPLA RALGPS2 RARDBP RBL1 RCAN1
RELN RFC1 RFC3 RFTN1 RGSL2 RUNX1 S100B SAMSN1 SASH1 SEL1L SEPT3 SERPINA1
SERPINA3 SERPINE1 SERPINF2 SGPL1 SH3PXD2A SHISA9 SNCA
SORCS1
SORCS2
SORCS3
SOS2
SSB SST STH SYN3 TAPBPL TARDBP TET1
TF
TFCP2
THEM5 THRA
TMEM63C TNK1 TP53
TP73
TRAF2
TRAK2 TRIM15
TRNG TRNH TRNQ TRNR TRNS2 TRNT TRPC4AP TTBK1
TTLL7
VCP VDR
VR22 WBSCR17 WWC1 YWHAZ ZBP1 ZNF155 ZNF224 ZNF225 C10orf112 C11orf30
C12orf41C1orf49 DNAJC28 C21orf63 LINC00472 FAM113B FAM63A LOC388458
LOC439999 LOC729993
- Need KEGG mapping ARC
CTNNA2
CYP17A1
.SLC8A1
KIAA1033
SNX1
SNX3
RAB7A
FRMD4A
PPP1R3B
.IMMP2L.
MX1
DRD4
SLC6A3
CREB1
MOBP
EIF2AK3
MBL2
TMEM106B
SLC2A14
USF1
NLRP3
NTF3
MZF1
PLD3
KIAA1462
FRMD4A
ABCG2
ARRB2
TREML2
PILRA
EXO3CL2
ARNTL2
. PLXNA4
IL23R
SETX
DNMT3B
GSAP
IL12A
IL12B
MYO18A
ANXA1
CDC25C
SUCLG2
MGST3
CYP17A2
. HSD17B10
TREM1
MMP9
SELE
NR1H3
PPP3R1
GRB10
DLGAP2
ZC3H12C
.GPR1
IL12A
IL12B
ZNF628
P2X7R
ASTN2
SLC40A1
ACO1
TFR2
KHDRBS2
CRYL1
CNTNAP4
TP53INP1
IGH
IRS1
FOXO3
MED23
IL28B
SQSTM1
TRIP4
SOD1
. HLA-DQB1
HCRTR2
SAR1B
EXOC3L2
UCP4
ARNTL
COBL
SLC10A2
- Risk Factors: In some cases the genes and risk factors can
be related and this is indicated by the red links
- Age is the greatest risk factor Keller,
2006
- Aluminium
exposure Perl
and Moalem, 2006
- Silica
levels in drinking water (Aluminium antidote) reduce the incidence of
Alzheimer's disease Gillette
et al, 2007
- plasma concentrations of manganese and total mercury were higher in
Alzheimer's disease. CSF concentrations of vanadium, manganese, rubidium,
antimony, cesium and lead were significantly lower Gerhardsson
et al, 2008
- Plasma levels of aluminium, cadmium, mercury and selenium were increased
and the contents of iron and manganese were lower in Alzheimer's disease
Basun
et al, 1991
- Dementia has been associated with anaemia Weuve
et al, 2013
- Serum cholesterol, ß- hexachlorocyclohexane and dieldrin are
risk factors for AD Singh
et al, 2012
- Association with
Diabetes Mellitus Kim
et al, 2010
- High blood glucose levels are associated with dementia even in
the absence of diabetes Crane
et al, 2013 High blood glucose levels have been linked to increased
protein glycation in the Alzheimer's disease brain Kassaar
et al, 2017
- Association with the metabolic
syndrome Razay
et al, 2007
- Family history of Parkinson's
disease ..Suhanov
et al, 2006
- Head injury predisposes to risk O'Meara
et al, 1997
- History of Manual work (occupational exposure) Fratiglioni
et al, 1993
- Loneliness Wilson
et al, 2007
- Organic
solvent exposure Kukull
et al, 1995
- "Exposure to air pollution causes neuroinflammation, an altered
brain innate immune response, and accumulation of Abeta42
and alpha-synuclein starting in childhood".Calderón-Garcidueñas.
et al,2008 and 2004
Immune-related
genes
- Higher maternal age at birth Fratiglioni,
1993
- Positively associated with the number of pregnancies Colucci
et al, 2006
- A longer duration of being breastfed may reduce the risk of developing
Alzheimer's disease in later life Fox
et al, 2013
- Hypertension
is a risk factor Skoog
and Gustafson, 2006
- Familial
aggregation (Alzheimer's disease in family members) Van
Duijn et al, 1991
- Concordance
in identical
twins = 59% Gatz
et al, 2006a 2006b
- Exposure to low frequency magnetic fields (in men) Qiu
et al, 2004
- Inverse association with smoking
.Van
Duijn and Hofman, 1991
- Prior exposure to anaesthesia
. Bohnen
et al, 1994
- Inverse association with cancer
, Roe
et al, 2005 Cell
cycle and DNA
Repair
- Carotid
artery atherosclerosis is a risk factor Van
Oijen et al, 2007 ..Shared
Atherosclerosis Genes
- Atherosclerosis in the Circle
of Willis , Beach
et al, 2007..Shared
Atherosclerosis genes
- High levels of good cholesterol (high density lipoprotein) are associated
with lower risk Reitz
et al, 2010
- Increased cardiovascular risk in midlife is linked to accelerated
cognitive decline as early as 10 years later Medscape
- Cerebral
embolism is a risk factor Purandare
et al, 2006
- Coronary artery disease is associated with Alzheimer's disease. Beeri
et al, 2006
- Hypoxia
related to cerebral
ischaemia and stroke
Zhang
& Le, 2009
- Non-Stroke Cardiovascular
disease . Eriksson
et al, 2010
- Previous major psychiatric illness Cooper
and Holmes, 1998
- Previous history of depression
. Fischer
et al, 2008
- Subclinical hyperthyroidism in the elderly increases the risk of dementia
and Alzheimer's disease.Kalmijn
et al, 2000
- An inverse association with rheumatoid arthritis, (or with the use
of non-steroidal anti-inflammatories used in arthritis ? ) McGeer
et al, 1999 : But a positive association in another study adjusting
for other variables: etanercept was associated with a decreased risk
of Alzheimer's disease in rheumatoid arthritis patients Chou
et al, 2016.
- Alzheimer's disease reportedly more prevalent in rheumatoid arthritis
patients , an effect reduced in those treated with the TNF antagonist
etanercept Chou
et al, 2016
- Seemingly benign factors (eyesight, hearing, denture wearing, stomach,
kidney, bladder or bowel problems, coughs and colds) as well as high
blood pressure and diabetes, constituting a frailty index, combine to
cumulatively and markedly increase the risk of Alzheimer’s disease
and dementia Song
et al, 2011
- A study, identifying physical inactivity, depression, smoking, mid-life
hypertension, mid-life obesity, low education and diabetes as key risk
factors, has estimated that ~ 50% of Alzheimer’s disease cases
may be preventable Barnes
and Yaffe, 2011
- Glaucoma
, cataract
and age-related
macular degeneration have been described as comorbid conditions
associated with Alzheimer's disease Kaczmarczyk
et al, 2007 glaucoma, age-related macular degeneration and diabetic
retinopathy also related to Alzheimer's disease in a large study, Lee
et al, 2018
- Neurosurgeons are a higher risk group for Alzheimer's disease Lollis
et al, 2010
- as were bank tellers, clergy, aircraft mechanics, and hairdressers
and dentists, exposure to 60 Hz magnetic fields and welding.(Alzheimer's)
or graders/sorters (non-agricultural), and clergy for presenile
dementia Park
et al, 2005
- an inherited pro-inflammatory cytokine profile in middle age is an
early risk factor Van
Exel et al, 2011
- shortened leukocyte telomere length is associated with risks for dementia
and mortality Honig
et al, 2012
- A high erythrocyte sedimentation rate (a marker of inflammation) has
been associated with Alzheimer's disease Li
et al, 2013
- Shorter sleep duration and poorer sleep quality are associated with
greater beta-amyloid burden Spira
et al, 2013 See also :- Sleep drives metabolite clearance from
the adult brain (via switching on the glymphatic
system) Xie
et al, 2013.
- A higher intake of fish, but not long-chain omega-3 fatty acids, has
been associated with a reduced risk of developing Alzheimer's disease
Wu
et al, 2015
- Exercise, statin, and fruit intake associated with lower risk for
AD mortality Williams,
2014.
- Ozone and particulate matter pollution have been associated with obesity,
diabetes and Alzheimer's disease-like pathology Calderón-Garcidueñas
et al, 2015 and with Parkinson's disease-like pathology Calderón-Garcidueñas
et al, 2016
- Meat, eggs and high fat dairy consumption linked to a higher risk
of Alzheimer's disease, dairy : Diets high in grains, fruit, vegetables
and fish associated with lower risk Grant,
2016
- Sauna bathing inversely associated with dementia and Alzheimer's disease
in middle-aged Finnish men .Laukkanen
et al, 2016
- Living near major roads associated with dementia Chen
et al,2017
- Higher intake of sugary beverages associated with magnetic resonance
imaging (MRI) markers of preclinical Alzheimer's disease Pase
et al, 2017
- Artificially sweetened soft drinks associated with an increased risk
of ischemic stroke, all-cause dementia, and Alzheimer’s disease
dementia.Pace
et al, 2017
- Atopy
(allergic hypersensitivity) is a risk factor and previous history
of Asthma
predicts shorter survival time Eriksson
et al, 2008 . Immune-related
- Autoimmune
diseases are common in Alzheimer's disease patents and their relatives
Frecker
et al, 1994 Immune-related
- Chlamydia
pneumoniae infection Gerard
et al, 2006
- Helicobacter
pylori : In infected patients H.Pylori eradication can have beneficial
effects on cognition Malaguarnera
et al, 2004 .Kounturas
et al, 2009
- Cryptococcal
meningitis
(C.Neoformans) has been mis-diagnosed as Alzheimer's disease in
two case reports, and dementia symptoms , following 3 year stays in
rest homes, were fully reversed by antifungal treatment Ala
et al, 2004.Hoffmann
et al, 2009
- Disseminated mycoses (fungal infections) observed in blood serum
from many Alzheimer's patients Alonso
et al, 2014.
- Cytomegalovirus
(Herpes virus HHV-5) Blasko
et al, 2007
- Alzheimer's disease has also been asociated with a combination
of HLA-BW15 and cytomegalovirus infection Renvoize
et al, 1979
- Increased inflammatory response in cytomegalovirus seropositive
patients with Alzheimer's disease : Westman
et al, 2014
- Herpes simplex (HSV-1)
and HHV-6
.Lin
et al, 2002 / Itzhaki
and Wozniak, 2006./Ball,
2006 .Licastro
et al, 2015. Viral
receptors
- Epstein-Barr virus and HHV-6 seropositivity may be environmental risk
factors for cognitive deterioration and progression to AD in the aged
Carbone
et al, 2013
- IgM antibodies to HSV-1 , indexing reactivation, predict the subsequent
development of Alzheimer's disease Letenneur
et al, 2008
- HIV-1
(AIDS:
NeuroAIDS) is often associated with dementia and can cause Alzheimer's
disease-like pathology Esiri
et al, 1998 .Power
et al, 2009
- HTLV-1 infection has been associated with dementia (case report) LycKe
et al, 1993
- Tooth loss and poor dental health (periodontitis)
has been linked to Alzheimer's disease. Caused
by P.Gingivalis, T.Denticola , S.Mutans and others Stein
et al, 2007 ./ Kim
et al, 2007.
- Antibodies to periodontal bacteria (A. actinomycetemcomitans,
P. gingivalis and T. forsythia) are able to discriminate between
Alzheimer's and normal patients Kamer
et al, 2009.
- Serum IgG antibody levels to periodontal microbiota are associated
with incident Alzheimer disease Noble
et al, 2014.
- Serum antibody levels to F nucleatum and P intermedia (periodontal
pathogens) found to be increased in Alzheimer's patients Sparks
et al, 2012
- Exposure to tuberculosis
has been reported as a risk factor in familial
Alzheimer's disease.Frecker
et al, 1994
- Toxoplasma Gondii IgG seropositivity was higher in Alzheimer's disease
patients Kusbeci
et al, 2010
- Hepatitis C infection has been associated with dementia Chiu
et al, 2013
- A combined infectious burden (Cytomegalovirus, HSV-1, Borrelia. burgdorferi,
C. pneumoniae and H. pylori is associated with Alzheimer's disease Bu
et al, 2014
- Serum tryptophan levels are decreased in Alzheimer's disease (a
marker of immune activation) Widner
et al, 2000 ..Immune-related
- An increase in the abundance of a pro-inflammatory gut microbiota
taxon, Escherichia/Shigella, and a reduction in the abundance of an
anti-inflammatory taxon, E. rectale possibly associated with a peripheral
inflammatory state in patients with cognitive impairment and brain amyloidosis
Cattaneo
et al, 2017.
- Beta-amyloid is broad spectrum antimicrobial peptide with activity
against bacteria and fungi Soscia
et al, 2010 and with antiviral properties against the Influenza
White
et al, 2014 and Herpes simplex viruses Bourgade
et al, 2014
- alpha-synuclein also has antimicrobial properties against bacteria
and fungi Park
et al, 2016 and acts as a restriction factor preventing viral transmission
from the peripheral to the central nervous system (West nile virus)
Massey
and Beckham, 2016 see also Beatman
et al, 2015
Pathogens detected in the Alzheimer's disease brain
- Herpes simplex (HSV-1) : Numerous studies have reported the presence
of HSV-1 in Alzheimer’s disease brains or an association with
HSV-1 seropositivity (reviewed
in Itzhaki et al, 2016)
- HHV-6 Present in a higher proportion of the AD than of age-matched
normal brain(70 vs 40%)
Lin et al, 2002
- Antibodies to Oral Treponema species have been detected at higher
frequency in the Alzheimer's disease brain Riviere
at al, 2002
- Herpes viruses HHV-6A and HHV-7 detected in Alzheimer's brains Redhead
et al, 2018
- The Epstein-Barr virus has been detected in a small percentage of
AD brains (6%). In aged individuals followed for 5 years EBV-positive
or HHV-6-positive peripheral blood leukocytes increased in those who
developed clinical AD Carbone
et al, 2014
- Propionibacterium acnes found in the Alzheimer's disease cortexKornhuber,
1992
- C.Pneumoniae has been detected in the Alzheimer's disease brain juxtaposed
to amyloid deposits and tangles Balin
et al, 1998 Hammond
et al, 2010
- Borrelia
Burgdorferi (Lyme
disease) Borrelia antigens colocalised with Amyloid plaques Miklossy
et al, 2004
- Filamentous micro-organisms, which may belong to the actinomycetes
found in Alzheimer's brains Howard
and Pilkington, 1992.
- Several spirochetes, including B. burgdorferi, and six periodontal
Treponemes (T.socranskii, T. pectinovorum, T.
denticola, T. medium, T.amylovorum and T. maltophilum) were detected
in the brains of Alzheimer's patients. These were able to promote beta-amyloid
deposition and tau phosphorylation in vitro Miklossy,
2011.
- Lipopolysaccharide from the oral pathogen Porphyromonas gingivalis
has been found in Alzheimer's brains post-mortem Poole
et al, 2013
- Rhamnolipids (bacterial components) have been identified in Alzheimer's
disease serum and CSF Andreadou
et al, 2017
- Lipopolysaccharide and E.coli K99 were detected in brain parenchyma
and vessels in all Alzheimer's disease and control brains. K99 levels
were greater in AD compared to control brains: K99 was localized to
neuron-like cells in AD but not control brains. LPS levels were also
greater in AD compared to control brain. LPS colocalized with Aß1-40/42
in amyloid plaques and with Aß1-40/42 around vessels in AD brains
Zhan
et al, 2016.
- Fungal/yeast species detected in the AD brain include: - Saccharomyces
cerevisiae; Malassezia globosa; Malassezia restricta; Penicillium Phoma
Alonso
et al, 2014, and C. famata, C. albicans. P. betae, and S. racemosum
Pisa
et al, 2015
- Antibodies to Candida famata, Candida albicans. Syncephalastrum racemosum
and Phoma betae stain corpora amylacea in the brains of Alzheimer’s
disease patients Pisa
et al, 2016
- Preliminary microbiome studies using unbiased next-generation sequencing
have also identified many fungi in AD brains (Alternaria, Botrytis,
Candida, Cladosporium, and Malassezia species) Alonso
et al, 2017
- Fungi (Alternaria, Botrytis, Candida, and Malassezia. )and bacteria
( Proteobacteria > Firmicutes, Actinobacteria, and Bacteroides )
found in AD brains Alonso
et al, 2018
- A pilot next-generation sequencing study identified several bacterial
species in both control and AD brains with an overall higher bacterial
load in AD, with a relatively higher proportion of Actinobacteria, and
notably Propionibacterium acnes Emery
et al, 2017
- Hepatitis B virus immunoreactivity found in Alzheimer's brains Mastroeni
et al, 2017
- Lipopolysaccharide progressively accumulates in neuronal parenchyma
preferentially associating with the periphery of neuronal nuclei Zhao
et al, 2017
- Human, fungal and bacterial proteins found in Corpora amylacea in
the AD brain Pisa
et al, 2018
Dietary and lifestyle factors
- Hyperhomocysteinemia
is a risk factor associated with AD and many other conditions Selhub
et al, 2006 ..
Homocysteine and folate
- S-adenosylmethione levels are low in the cerebrospinal fluid Linnebank
et al, 2010
- High folate
intake related to lower incidence of Alzheimer's disease Luchsinger
et al, 2007 Folate-related
- Mild hypercholesterolaemia
/ Pappolla
et al, 2003 Cholesterol-related
- Saturated
fat intake increases the risk of dementia and Alzheimer's disease
Laitinen
et al, 2003 Cholesterol
related
- Higher calorific and fat intake reported to increase the risk of developing
Alzheimer's disease Luchsinger
et al, 2002 Cholesterol-related
- "Physical inactivity, dietary fat intake, alcohol drinking, and
smoking at midlife are associated with the risk of dementia and AD,
especially among APOE4
carriers" Kivipelto
et al, 2008
- "Moderate intake of unsaturated
fats at midlife is protective, whereas a moderate intake of saturated
fats may increase the risk of dementia and AD, especially among
ApoE epsilon4
carriers".Laitinen
et al, 2006 Cholesterol-related
- Inverse association with coffee
drinking Quintana
et al, 2007
- A high carbohydrate diet has been linked to Alzheimer's disease risk
Seneff
et al, 2011
- Midlife obesity
. Whitmer
et al, 2007
- Waist to hip ratio (central obesity) has been implicated as a risk
factor Luchsinger
et al, 2011
- Nonsteroidal
anti-inflammatory drugs, wine consumption, coffee consumption, and
regular physical activity associated with a reduced risk of Alzheimer's
disease Lindsay
et al, 2002
- Reduced incidence of Alzheimer's disease has also been reported in
relation to the use of H2 histamine receptor antagonists Anthony
et al, 2000 .. Immune-related
genes
- Angiotensin receptor blockers may be associated with a reduced risk
of dementia in high vascular-risk individuals Chiu
et al, 2014
- Angiotensin converting enzyme inhibitors have been reported to be
associated with a slower rate of cognitive decline in Alzheimer's disease
independently of effects on hypertension Soto
et al, 2013
- An active and socially integrated lifestyle in later life may protect
against Alzheimer's disease and dementia Fratiglioni
et al, 2004
- Pesticide exposure may increase the risk of developing Alzheimer's
diseases Hayden
et al, 2010 Pesticide
and disease database
- High levels of dichlorodiphenyldichloroethylene (DDE), the metabolite
of the pesticide dichlorodiphenyltrichloroethane (DDT) have been associated
with Alzheimer's disease Singh
et al, 2013 an effect increased in those with the APOE4 allele Richardson
et al, 2014
Hormonal effects
- Related to age-related loss of sex steroid hormones in both women
and men Pike
et al, 2009
- Testosterone
has been reported to have protective effects
RSS feed
- Oestrogen
has been reported to have protective effects Craig
and Murphy, 2010
- However:- Oestrogen plus progestin
therapy increased the risk for probable dementia in postmenopausal women
aged over 65 Schumaker
et al, 2003
- Luteinising
hormone releasing hormone has been reported to reduce the risk of
developing Alzheimer's disease in men D'Amico
et al, 2010
- Insulin-like
growth factor, Vascular
endothelial growth factor and
transforming growth factor beta levels have been reported to be
reduced in blood cell extracts Luppi
et al, 2009
- Plasma levels of tryptophan and kynurenic acid are decreased with
an increase in Quinolinic acid levels Gulaj
et al, 2010
- 24-Hydroxycholesterol plasma levels are reduced, correlating with
brain atrophy Leoni
and Caccia, 2011
- Low CSF levels of S-adenosyl-methionine have been reported in Alzheimer's
disease Linnebank
et al, 2010
- High plasma levels of neopterin have been reported (peripheral immune
activation) Parker
et al, 2012
Autoantibodies present in Alzheimer's
disease sera
- Beta-amyloid antibodies are found in the ageing population Sohn
et al, 2009 and in Alzheimer's disease Gustaw-Rothenberg
et al, 2010 which can increase beta-amyloid toxicity
Nath et al, 2003
- Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis
in C57/BL6 mice.Furlan
et al, 2003
- Antibodies to neurofibrillary tangles Kingsley
et al, 1988
- Vaccination with tau in mice induces histopathologic features
of Alzheimer disease, including neurofibrillary tangle-like struvtures,
axonal damage, and gliosis
Rosenmann et al, 2006.
- AGER antibodies to the receptor for advanced glycation end products
Mruthinti
et al, 2006
- Catalytic autoantibodies to beta-amyloid in the ageing population
Paul
et al, 2010
- ATP synthase
Vacirca et al, 2010 These antibodies increase the cellular uptake
of HDL Vacirca
et al, 2011
- Cholinergic receptor autoantibodies (CHRNA7) possibly formed from
common infections and destruction of the respiratory epithelium Koval
et al, 2011
- Bradykinin antibodies Myagkova
et al, 2003
- Dopamine and serotonin antibodies Davydova
et al, 2002
- anti-cyclic citrullinated peptide antibody Satoh
et al, 2010
- Glutamate autoantibodies Davydova
et al, 2009
- heparan sulfate proteoglycan antibodies
Fillit et al, 1987
- Histone autoantibodies Mecocci
et al, 1993
- MBP autoantibodies Singh,
1994
- NGF antibodies Roy
et al, 1988
- NGF antibodies expressed only in lymphocytes cross the blood brain
barrier causing cholinergic loss, tau hyperphosphorylation, and
beta-amyloid deposition in mice Capsoni
et al, 2010
- PTCD2 pentatricopeptide repeat domain 2 Acharya
et al, 2012
- SRPK1 autoantibodies Daniilidou
et al, 2011
- Low levels of phosphorylcholine antibodies Eriksson
et al, 2010
- Redox-reactive antiphospholipid antibody McIntyre
et al, 2009
- thyroid microsomal antigens Gut
et al, 2009
- Antibodies to oxidised low density lipoprotein Kankaanpää
et al, 2009
- Antibodies against GM1 ganglioside in dementia patients Hatzifilippou
et al, 2008 and in Alzheimer's disease Chapman
et al, 1988
- antibodies to S100B Gruden
et al, 2007
- Antibodies to lysozyme Gruden
et al, 2004
- Anti phospholipid antibodies Mosek
et al, 2000
- Anti microglial antibodies Lemke
et al, 1999
- anti tubulin and GFAP antibodies Terryberry
et al, 1998
- Anti brain spectrin Fernández-Shaw
et al, 1997
- Spectrin, peroxidase and thyroglobulin and HSV-1 Ounanian
et al, 1990
- Anti hippocampal antibodies
Loeffler et al, 1997
- .Brain and erythrocyte anion transporter protein, band 3 antibodies
Kay et al, 1997
- Alzheimer's disease CSF specifically stains activated microglia and
neural macrophages McRae
et al, 1996
- Antibodies against heavy neurofilament NEFH Soussan
et al, 1994 and neurofilaments Zavalishin
et al, 1988
- Choroid plexus autoantibodies Serot
et al, 1992
- Platelet antibodies in dementia Shinitzky
et al, 1991
- Prolactin cell antibodies Pouplard
et
al, 1983
- alpha 2-glycoprotein Groppa
and Chekhonin 1991]
- cholinergic neurons identified by Alzheimer's disease CSF antibodies
Dahlstrom
et al, 1990 which causes immunolysis of cholinergic synaptosomes
Foley
et al, 1988
- Antibodies to spectrin, peroxidase, and thyroglobulin
Ounanian et al, 1990
- Antibodies to serotonin, melatonin, and the metabolites 5-HIAA, and
5-methoxytryptophol as well as to kynurenic acid , 3-hydroxy kynurenic
acid, Quinolinic acid, Anthralinic acid, 3-hydroxy anthralinic acid,
picolinic acid Duleu
et al, 2010
- Diagnosis of Alzheimer’s Disease Based
on Disease-Specific Autoantibody Profiles in Human Sera Nagele
et al, 2011
- The 10 autoantibodies used to diagnose Alzheimer's disease
- FRMD8 FERM domain containing 8
- PTCD2 Pentatricopeptide repeat domain 2
- C9orf9
- LGALS1 Lectin, galactoside-binding, soluble, 1 (galectin 1)
- POMC Proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/
alphamelanocyte
stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)
MAPKAPK5 Mitogen-activated protein kinase-activated protein kinase
5
- CENTA2 Centaurin, alpha 2
- DNAJC8 DnaJ homolog subfamily C member 8
- ANKHD1 Ankyrin repeat and KH domain containing 1
- MRPL34 Mitochondrial ribosomal protein L34 nuclear gene
encoding mitochondrial protein
- See also "Application of immunosignatures to the assessment of
Alzheimer's disease".(randomly generated 20mer peptides from phage
display) Restrepo
et al, 2011
Epidemiological studies
- Alzheimer's disease is more common in women Schmidt
et al, 2008
- In the USA, Alzheimer's disease is more common in Afro-Americans and
Hispanics than in European Americans Alzheimer's
association 2010
- Illiteracy is associated with a higher risk of AD, an effect increasing
with age Lee
et al, 2008.
- Low educational attainment is associated with a higher risk of Alzheimer's
disease Letenneur
et al, 1999
- Being a farmer may increase the risk of dementia with parkinsonism
in women Helmer
et al, 2001
- Having fathers as coal miners hs been associated with Alzheimer's
disease Whalley
et al, 1995
- An association between goods production, manual work and Alzheimer's
disease was found in Korea Qiu
et al, 1993
- Birth in a rural area has been asociated with Alzheimer's disease
Jean et al, 1996
- Long-term occupational exposure to a higher
Extremely-low-frequency magnetic field level may increase the risk
of Alzheimer's disease and dementia in men Qiu
et al, 2004
- In the Nun
study, despite Alzheimer's disease pathology (plaques
and tangles)
cognitive function can be normal Snowdon,
1997 Nun study at the
University of Minnesota
- Cognitive decline leading to dementia can be observed in Bipolar disorder
Lebert
et al, 2008
- Early dementia is often diagnosed as some form of psychiatric disease
(depression, schizophrenia, bipolar etc.) and these (or the drugs used
to treat them ?) might also be independent risk factors for the subsequent
development of neurodegenerative diseases Wooley
et al, 2011
- The use of benzodiazepines has been associated with dementia risk
Lucchetta
et al, 2018
- Higher cumulative anticholinergic use is associated with an increased
risk for dementia (mostly certain tricyclic antidepressants, first-generation
antihistamines, and bladder antimuscarinics) Gray
et al, 2015.
- Death of a spouse without remarriage can increase the risk of dementia
Medscape
- A high level of magnetic iron particles has been found in the Alzheimer's
disease brain Pankurst
et al, 2008
Protective Drugs, Diets Vitamins and Vaccines (Clinical
Trials)
- The Mediterarranean
diet may reduce the risk of developing Alzheimer's disease Scarmeas
et al, 2006
- Garlic may reduce the risk of dementia and cardiac disease Borek,
2006
- Fruit and vegetable juices may delay the onset of Alzheimer's disease
Dai
et al, 2006
- Cereal consumption may reduce the risk of developing Alzheimer's disease
Grant,
1999
- Moderate consumption of red wine may delay the onset of Alzheimer's
disease Panza
et al, 2004
- High dietary intake of vitamin
C and vitamin
E may lower the risk of developing Alzheimer's disease.Engelhart
et al, 2002
- Vitamin D deficiency has been associated with Alzheimer's disease
Pogge, 2010: genetically decreased vitamin D levels associated with
Alzheimer disease Mokry
et al, 2016
- High plasma levels of Vitamin
E are associated with reduced risk Mangialasche
et al, 2010
- Vitamin
B12 may delay the onset of Alzheimer's disease Newsflash
Hoosmann
et al, 2010
- Fish
consumption and intake of n-3
polyunsaturated fatty acids may reduce the incidence of Alzheimer's
disease Morris
et al, 2003
- Non-steroidal
anti-inflammatories may reduce the incidence of Alzheimer's disease
McGeer
et al, 2006 .. Immune-related
genes
- Statins
may reduce the incidence of Alzheimer's disease Wolozin
et al, 2000 .. Cholestrerol-related
genes
- Antihypertensives
(calcium
antagonists) may reduce the risk of dementia in hypertensive patients
Forette
et al, 2002
- Exposure to vaccines against diphtheria
or tetanus,
poliomyelitis
and influenza
associated with lower risk for Alzheimer's diseaseVerreault
et al, 2002
- Low serum levels of Vitamin A and beta-carotene in Alzheimer's disease
Jimenez
et al, 1999
- Low levels of Vitamin K in Alzheimer's disease Presse
et al, 2008
- Low dietary niacin has been associated with Alzheimer's disease Morris
et al, 2004
- Folic acid, vitamin B12 and vitamin B6 lower homocysteine levels and
slowed cognitive and clinical decline in people with mild cognitive
impairment , in particular in those with elevated homocysteine de
Jager et al, 2011 and slow the rate of brain atrophy Smith
et al, 2010
Biomarkers
- A blood RNA signature highlights genes involved in pathways associated
with macrophages and lymphocytes: TGF-beta signaling, oxidative stress,
innate immunity and inflammation, cholesterol homeostasis, and lipid-raft
perturbation pathways were implicated Fehlbaum-Beurdeley
et al, 2010
- 10 autoantibody biomarkers can differentiate Alzheimer's disease sera
Nagele
et al, 2011
- An immunosignature derived from thousands or randomly synthesised
peptides is able to accurately discriminate Alzheimer's disease Restrepo
et al, 2011
- An algorithm derived from a biomarker risk score, clinical lab (glucose,
triglycerides, total cholesterol, homocysteine), and demographic (age,
gender, education, APOE*E4 status) data O'Bryant
et al, 2011.
- Decreased plasma desmosterol levels Sato
et al, 2011 and reduced desmosterol/cholesterol ratio Sato
et al, 2012
- Increased plasma levels of annexin ANXA5 Sohma
et al, 2013
- Higher serum phenylalanine concentrations related to immune activation
observed in a subgroup of AD patients Wissmann
et al, 2013.
- High levels of beta-defensin DEFB1 (anti-microbial peptide ) in the
AD brain Williams
et al, 2013
- Higher tryptophan 2,3 dioxygenase (TDO) and indoleamine 2,3 dioxygenase
1 (IDO1) immunoreactivity in Alzheimer's disease hippocampus where TDO
co-localizes with quinolinic acid, neurofibrillary tangles, tau and
amyloid deposits Wu
et al, 2013 The IDO1 reponse is a common defense mechanism against
pathogens that depend upon the host supply of tryptophan, and is also
involved in antiviral effects) Reviewed in Murakami
et al, 2013
- Significant increase was observed with progression of disease in serum
levels of choline, creatinine, asymmetric dimethyl-arginine, homocysteine-cysteine
disulfide, phenylalanyl-phenylalanine, and different medium chain acylcarnitines.
Asparagine, methionine, histidine, carnitine, acetyl-spermidine and
C5-carnitine were reduced González-Domínguez
et al, 2014.
- Evidence for disruption of the choroid plexus epithelium Bergen
et al, 2015
- 24-hydroxycholesterol and 27-hydroxycholesterol are elevated in Alzheimer's
and mild cognitive impairment subjects Wang
et al, 2016
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