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46/100

✓ Peer-reviewed alzhub usefulness score 46 out of 100. TREM2 and immune genetics

Topic: Amyloid, tau and blood-test diagnosis

Plain-language summary

The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD.

What this study adds

Evidence grade: Low

This is a narrative review. This paper proposes a model in which Alzheimer's disease may originate in the periphery, involving APOE ε4, altered miRNA expression, and epigenetic dysregulation of TREM2. It is a proposed model and does not test any treatment, cure, or prevention.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Morris, G., Berk, M., Maes, M., & Puri, B. K. (2019). Could Alzheimer's Disease Originate in the Periphery and If So How So? Molecular neurobiology. https://doi.org/10.1007/s12035-018-1092-y

Vancouver

Morris G, Berk M, Maes M, Puri BK. Could Alzheimer's Disease Originate in the Periphery and If So How So? Molecular neurobiology. 2019. doi:10.1007/s12035-018-1092-y. PMID: 29705945.

BibTeX

@article{morris2019-29705945,
  author  = {Morris, G. and Berk, M. and Maes, M. and Puri, B. K.},
  title   = {{Could Alzheimer's Disease Originate in the Periphery and If So How So?}},
  journal = {Molecular neurobiology},
  year    = {2019},
  doi     = {10.1007/s12035-018-1092-y},
  pmid    = {29705945},
  url     = {https://doi.org/10.1007/s12035-018-1092-y}
}

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How to read this study

Design: this is a narrative review. It summarises a field without a fixed search method, so it shows how authors read the evidence rather than measuring it. Use it to find the primary studies, not as a result in itself.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Here, an alternative molecular neurobiological model is proposed.
It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD.
In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 expression, with subsequent changes in miR-486 leading to altered levels of protein kinase B (Akt), mechanistic (previously mammalian) target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), all of which play major roles in microglial activation, proliferation and survival, there is activation of microglia, leading to the subsequent (further) production of cytokines, chemokines, nitric oxide, prostaglandins, reactive oxygen species, inducible nitric oxide synthase and cyclooxygenase-2, and other mediators of inflammation and neurotoxicity.
These changes are associated with the development of amyloid and tau pathology, mitochondrial dysfunction (including impaired activity of the electron transport chain, depleted basal mitochondrial potential and oxidative damage to key tricarboxylic acid enzymes), synaptic dysfunction, altered glycogen synthase kinase-3 (GSK-3) activity, mTOR activation, impairment of autophagy, compromised ubiquitin-proteasome system, iron dyshomeostasis, changes in APP translation, amyloid plaque formation, tau hyperphosphorylation and neurofibrillary tangle formation.

Why it matters

This paper proposes a model in which Alzheimer's disease may originate in the periphery, involving APOE ε4, altered miRNA expression, and epigenetic dysregulation of TREM2. It is a proposed model and does not test any treatment, cure, or prevention.

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Study details

Evidence strengthLow

How this study scored 46/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Molecular neurobiology)
Journal's citation record	2 / 4	Molecular Neurobiology: journal h-index 176 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2019 — within 10 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 84 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	9.3 citations a year over 9 year(s) since 2019
Impact for its field and year	3 / 6	Cited 6.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	2 / 4	Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Basant K. Puri: h-index 59 (OpenAlex, whole career)
Institution's track record	2 / 3	Imperial College London: institution h-index 1,744 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 9 institution(s) in 3 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 29705945)
Free to read	2 / 2	Free to read
Total	46 / 100	—

What each of these 20 components measures, and what this score is not →

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