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Environmental and other risk factors affecting Alzheimer's disease .......... Alzheimer's disease associations and societies worldwide

An interesting article "Can Alzheimer's disease be prevented" can be found at the National Institute on ageing website. It is not yet possible to cure Alzheimer's disease. However there is reasonable evidence to suggest that a healthy lifesyle, "sensible" dietary regimes and avoidance of excess (smoking and alcohol) can delay the onset of the disease. This really simplifies to " a healthy mind in a healthy body" Mens sana in corpore sano. These lifestyle issues are similar, if not identical to the problems of heart disease, atherosclerosis and stroke. Advice on these matters can also be found at the American Heart Association and at the Alzheimer's Association websites and at PredictAD or Food For The Brain at Alzheimer's Disease International and at Dementia Today

Ongoing clinical trails, worldwide, can be interrogated at ClinicalTrials.Gov a service of the US National Institutes of Health

  • Papers based on this site: Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis Neurochem Int ,2006
  • Interactions between the products of the Herpes simplex genome and Alzheimer's disease susceptibility genes: relevance to pathological-signalling cascades.Neurochem Int, 2007
  • Alzheimer's disease as an autoimmune and potentially curable disorder ?NaturePrecedings and Website (with translation and enhanced links)
  • APP, APOE, complement receptor 1, clusterin and PICALM and their involvement in the herpes simplex life cycle. Neuroscience Letters, 2010
  • Alzheimer's disease plaques and tangles: Cemeteries of an immune battle with herpes simplex Neurochem.Int, 2010 Tangles description from TauRX therapeutics
  • Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner Int .J.Alz Dis 2010
  • The fox and the rabbits, environmental variables and population genetics.1: Replication problems in association studies and the untapped power of GWAS. 2: Vitamin A deficiency, herpes simplex reactivation and other causes of Alzheimer’s disease ISRN Neurology, 2011
  • Alzheimer’s disease: APP, gamma secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1 and MS4A2, and their relationships with herpes simplex , C.Pneumoniae, other suspect pathogens and the immune system: Int.J.Alz.Dis, 2011
  • Toxoplasmosis and polygenic diseases: Extensive T.Gondii host/pathogen interactome enrichment in nine psychiatric or neurological disorders J.Pathogens, 2012
  • Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders Pathogens and disease 2013.
  • Microbes and Alzheimer's disease Journal of Alzheimer's disease, 2016
  • Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease JAD reports , 2017
  • Kegg pathway analysis of over 400 susceptibility genes: Herpes simplex related genes are included.

Infectious agents Alzforum Herpes/Alzheimers webinar

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

Hormonal effects

Autoantibodies present in Alzheimer's disease sera

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)


  • 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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Last update: August 14, 2018