The Historical Development of the Pathological Changes in Alzheimer’s Disease Based on Microbiology, Anatomy, and Physiology

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Herbert B. Allen, MD Rachel A. Allen, BA


The major pathological changes in Alzheimer’s disease were found in hippocampal specimens from Alzheimer disease patients. We contend that spirochetal bacteria that make biofilms cause these changes. The spirochetal/biofilm complexes induce the changes of note including neurofibrillary tangles, senile plaques, beta amyloid, and atrophy. It has been shown previously that when spirochetes make biofilms, they create beta amyloid simultaneously. When the biofilm is made intracellularly (in the neuron), the beta amyloid that is also produced, interacts with tau protein and converts it to hyperphosphorylated tau. This leads directly to neurofibrillary tangles. Produced extracellularly (outside the neuron), the biofilms, which are coated by beta amyloid, form the senile plaques. The interaction of the biofilm in the senile plaques with the innate immune system molecule Toll-like receptor 2 produces beta amyloid by known pathways. The atrophy, both total and regional, is produced when the neurons disintegrate.  All these pathological findings take considerable time that fits with the clinical course of the disease. For instance, it takes up to two years for spirochetes to make a single biofilm. This differs from other microbes such as Chlamydia pneumoniae, Porphyromonas gingivalis, and Herpes simplex that make biofilms in minutes. The long time for development therefore fits better with spirochetes compared to other organisms.

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ALLEN, Herbert B.; ALLEN, Rachel A.. The Historical Development of the Pathological Changes in Alzheimer’s Disease Based on Microbiology, Anatomy, and Physiology. Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 17 june 2024. doi:
Research Articles


1) Allen HB (2021) Alzheimer’s Disease: A Chronic Infection. DOI: 10.9734/bpi/mono/978-81-9479-7-5
2) MacDonald AB (1986) Borrelia in the brains of patients dying with dementia. JAMA 256, 2195-2196.
3) Riviere GR, Riviere GH, Smith KS (2002) Molecular and immunological evidence of oral treponemes in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol 17, 113-118.
4) Miklossy J (2011) Emerging roles of pathogens in Alzheimer disease. Expert Reviews in Molecular Medicine e30 DOI:
5) Miklossy J (2011) Alzheimer’s Disease – A Neurospirochetosis. Analysis of the evidence following Koch’s and Hill’s Criteria. J Neuroinflammation. 8:90.
6) Miklossy J. Historic evidence to support a causal relationship between spirochetal infections and Alzheimer’s disease. Front Aging Neurosci. 2015; 7:46.
7) Macdonald AB (2015) biofilms-coated with beta amyloid Accessed 15 June 2016
8) Tukel C, Wilson RP, Nishimori M, Pezeshki M, Chromy BA, Baumier AJ (2009) Responses to Amyloids of Microbial and Host Origin are mediated through Toll-like Receptor 2. Cell Host Microbe. 2009; 6: 45-53.
9) Miklossy J. Bacterial Amyloid and DNA are Important Constituents of Senile
10) Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques. J Alz Dis. 2016; 53: 1459-1473.
11) Tasneem U, Yasin N, Qasim M, et al. Biofilm producing bacteria: A serious threat to public health in developing countries. J Food Sci Nutr. 2018;1(2):25-31.
12) Allen HB. Alzheimer’s Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-β with Regard to Potential Treatment and Prevention. J Alz Dis. 2016; 53(4), 1271–1276.
13) Itzhaki RF, Lin W-F, Shang D, Wilcock GK, Faragher B, Jamieson GA. (1997) Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet 349: 241–44
14) Singhrao SK, Harding A, Poole S, Kesavalu L, Crean S. Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer's Disease. Mediators Inflamm. 2015;2015:137357. doi: 10.1155/2015/137357. Epub 2015 Apr 30.
15) Balin BJ, Gérard HC, Arking EJ, Appelt DM, Branigan PJ, Abrams JT, Whittum-Hudson JA, Hudson AP. Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Med Microbiol Immunol. 1998 Jun;187(1):23-42. doi: 10.1007/s004300050071. PMID: 9749980.
16) Allen HB (2020): Essential role of biofilms in Alzheimer's Disease. figshare.J contribution
17) Miklossy J (2016). Bacterial Amyloid and DNA are Important Constituents of Senile Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques. J Alz Dis 53: 1459-1473.
18) Allen HB, Allawh R, Touati A, Katsetos C, Joshi SG. Alzheimer’s Disease: The Novel Finding of Intracellular Biofilms. 2017; 8:247. J Neuroinfect Dis.
19) Doyle KP, Quach LN, Sol´e M, Axtell RC, Nguyen TV, Soler-Liavena GJ, Jurado S, Han J, Steinman L, Longo FM, Schneider JA, Malenka RC, Buckwalter MS (2015) B-lymphocyte mediated delayed cognitive impairment following stroke. J Neurosci 35, 2133-2145.
20) Iqbal K, Alonso AC, Chen S, Chohan MO, El-Akkad E, Gong C Khatoon S, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739: 198-210.
21) Zempel H, Thies E, Mandelkow E, et al. Aβ Oligomers Cause Localized Ca2 Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines. J Neurosci. 2010; 30: 11938-11950.
22) Allen HB (2021) A Novel Approach to the Treatment and Prevention of Alzheimer’s Disease Based on the Pathology and Microbiology. J Alz Dis 84(1): 61-67.
23) Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer’s disease-associated β-protein is an anti-microbial peptide. PLoS ONE. 2010; 25(3):e9505.doi:10.1371/journal.pone.0009505.
24) Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012;344e977.
25) Allen HB, Joshi SG. Nicotine and Alzheimers Disease: Mechanism for How the Fog of Smoke Increases the Fog of Dementia. J Neuroinfect Dis. 2016; 7: 237.
26) Allen HB, Husienzad L, Joshi SG. The Impact of Diabetes on Alzheimer’s disease. J Alz Dis. 2016. 6 Sept.