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Molecular and cellular pathophysiology of preclinical Alzheimer's disease
Mufson EJ, Ikonomovic MD, Counts SE, Perez SE, Malek-Ahmadi M, Scheff SW, Ginsberg SD.. Behavioural brain research, 2016-05-13
Topic: Amyloid, tau and blood-test diagnosis
Although the two pathological hallmarks of Alzheimer's disease (AD), senile plaques composed of amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau, have been studied extensively in postmortem AD and relevant animal and cellular models, the pathogenesis of AD remains unknown, particularly in the early stages of the disease where therapies presumably would be most effective. We and others have demonstrated that Aβ plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia. In this regard, aged people with no cognitive impairment (NCI), mild cognitive impairment (MCI, a presumed prodromal AD transitional state, and AD all present at autopsy with varying levels of pathological hallmarks. Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Aβ plaques. However, correlations are even higher between cognitive decline and synaptic loss. In this review, we illustrate relevant clinical pathological research in preclinical AD and throughout the progression of dementia in several areas including Aβ and tau pathobiology, single population expression profiling of vulnerable hippocampal and basal forebrain neurons, neuroplasticity, neuroimaging, cerebrospinal fluid (CSF) biomarker studies and their correlation with antemortem cognitive endpoints. In each of these areas, we provide evidence for the importance of studying the pathological hallmarks of AD not in isolation, but rather in conjunction with other molecular, cellular, and imaging markers to provide a more systematic and comprehensive assessment of the multiple changes that occur during the transition from NCI to MCI to frank AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mufson, E. J., Ikonomovic, M. D., Counts, S. E., Perez, S. E., Malek-Ahmadi, M., Scheff, S. W., et al. (2016). Molecular and cellular pathophysiology of preclinical Alzheimer's disease. Behavioural brain research. https://doi.org/10.1016/j.bbr.2016.05.030
Vancouver
Mufson EJ, Ikonomovic MD, Counts SE, Perez SE, Malek-Ahmadi M, Scheff SW, et al. Molecular and cellular pathophysiology of preclinical Alzheimer's disease. Behavioural brain research. 2016. doi:10.1016/j.bbr.2016.05.030. PMID: 27185734.
BibTeX
@article{mufson2016-27185734,
author = {Mufson, E. J. and Ikonomovic, M. D. and Counts, S. E. and Perez, S. E. and Malek-Ahmadi, M. and Scheff, S. W. and Ginsberg, S. D.},
title = {{Molecular and cellular pathophysiology of preclinical Alzheimer's disease}},
journal = {Behavioural brain research},
year = {2016},
doi = {10.1016/j.bbr.2016.05.030},
pmid = {27185734},
url = {https://doi.org/10.1016/j.bbr.2016.05.030}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- We and others have demonstrated that Aβ plaques and NFTs are present in varying degrees before the onset and throughout the progression of dementia.
- Cognitive decline, a requisite for the clinical diagnosis of dementia associated with AD, generally correlates better with NFTs than Aβ plaques.
Why it matters
This review describes how amyloid plaques and neurofibrillary tangles are present in varying degrees before and throughout dementia progression, and notes that cognitive decline correlates better with tangles than plaques, and even better with synaptic loss. It summarizes research into the early stages where therapies would presumably be most effective, but presents no treatment or cure.
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 (Behavioural brain research) |
| Journal's citation record | 3 / 4 | Behavioural Brain Research: journal h-index 252 (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 | 1 / 5 | 2016 — within 20 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 | 5 / 7 | Cited 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.7 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 4 / 6 | Cited 12.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Stephen D. Ginsberg: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27185734) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
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