Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov;19(11):5209-5231.
doi: 10.1002/alz.13076. Epub 2023 Jun 7.

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration

Richard Lathe  1 , Nikki M Schultek  2 , Brian J Balin  3 , Garth D Ehrlich  4 , Lavinia Alberi Auber  5   6 , George Perry  7 , Edward B Breitschwerdt  8 , David B Corry  9 , Richard L Doty  10 , Robert A Rissman  11 , Peter L Nara  12 , Ruth Itzhaki  13 , William A Eimer  14   15   16 , Rudolph E Tanzi  14   15   16 ; Intracell Research Group Consortium Collaborators
Collaborators, Affiliations
Review

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration

Richard Lathe et al. Alzheimers Dement. 2023 Nov.

Abstract

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

Keywords: Alzheimer's disease; antimicrobial; antiviral; bioinformatics; blood; cerebrospinal fluid; collaboration; dementia; diagnosis; methodology; microbiome; mild cognitive impairment; olfactory neuroepithelium; pathobiome; polymerase chain reaction; protocol; sequencing.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest

Declaration of interests: none

Figures

FIGURE 1.
FIGURE 1.
The antimicrobial hypothesis of Alzheimer's disease (AD). Genetic and/or physiological predisposition facilitates microbial infection and proliferation, leading to Aβ production – a defense mechanism to entrap and inactivate microbes – as well as to aggregation of Tau tangles, further local inflammation, and neuronal death, culminating in AD.
FIGURE 2.
FIGURE 2.
Microbes and the brain: routes of entry. Figure courtesy of Noeen Malik. Abbreviation: CSF, cerebrospinal fluid.
FIGURE 3.
FIGURE 3.
Flow chart of the Alzheimer's Pathobiome Initiative. Abbreviations: AD, Alzheimer's disease; CSF, cerebrospinal fluid; DD, digital droplet; EM, electron microscopy; eToL, electronic tree of life; FISH, fluorescence in situ hybridization; RT, reverse transcription.
See this image and copyright information in PMC

References

    1. Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H, Bullido MJ, Carter C, Clerici M, Cosby SL, Del TK, Field H, Fulop T, Grassi C, Griffin WS, Haas J, Hudson AP, Kamer AR, Kell DB, Licastro F, Letenneur L, Lovheim H, Mancuso R, Miklossy J, Otth C, Palamara AT, Perry G, Preston C, Pretorius E, Strandberg T, Tabet N, Taylor-Robinson SD, Whittum-Hudson JA. Microbes and Alzheimer's disease. J.Alzheimers.Dis 2016;51:979–984. - PMC - PubMed
    1. Strittmatter WJ, Roses AD. Apolipoprotein E and Alzheimer's disease. Annu.Rev.Neurosci 1996;19:53–77. - PubMed
    1. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002;297:353–356. - PubMed
    1. Largent EA, Peterson A, Lynch HF. FDA drug approval and the ethics of desperation. JAMA Intern.Med 2021;181:1555–1556. - PMC - PubMed
    1. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 2010;5:e9505. - PMC - PubMed