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A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease
Swerdlow RH, Khan SM.. Medical hypotheses, 2004-01-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) includes etiologically heterogeneous disorders characterized by senile or presenile dementia, extracellular amyloid protein aggregations containing an insoluble amyloid precursor protein derivative, and intracytoplasmic tau protein aggregations. Recent studies also show excess neuronal aneuploidy, programmed cell death (PCD), and mitochondrial dysfunction. The leading AD molecular paradigm, the "amyloid cascade hypothesis", is based on studies of rare autosomal dominant variants and does not specify what initiates the common late-onset, sporadic form.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Swerdlow, R. H., & Khan, S. M. (2004). A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Medical hypotheses. https://doi.org/10.1016/j.mehy.2003.12.045
Vancouver
Swerdlow RH, Khan SM. A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Medical hypotheses. 2004. doi:10.1016/j.mehy.2003.12.045. PMID: 15193340.
BibTeX
@article{swerdlow2004-15193340,
author = {Swerdlow, R. H. and Khan, S. M.},
title = {{A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease}},
journal = {Medical hypotheses},
year = {2004},
doi = {10.1016/j.mehy.2003.12.045},
pmid = {15193340},
url = {https://doi.org/10.1016/j.mehy.2003.12.045}
}
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Key findings
- Recent studies also show excess neuronal aneuploidy, programmed cell death (PCD), and mitochondrial dysfunction.
- The leading AD molecular paradigm, the "amyloid cascade hypothesis", is based on studies of rare autosomal dominant variants and does not specify what initiates the common late-onset, sporadic form.
- We propose for late-onset, sporadic AD a "mitochondrial cascade hypothesis" that comprehensively reconciles seemingly disparate histopathologic and pathophysiologic features.
- In our model, the inherited, gene-determined make-up of an individual's electron transport chain sets basal rates of reactive oxygen species (ROS) production, which determines the pace at which acquired mitochondrial damage accumulates.
Why it matters
This paper proposes a 'mitochondrial cascade hypothesis' for late-onset sporadic Alzheimer's disease, citing excess neuronal aneuploidy, programmed cell death and mitochondrial dysfunction, and noting that the amyloid cascade hypothesis does not specify what initiates the common sporadic form. It is a proposed hypothesis and reports no treatment, cure or prevention.
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 randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Medical hypotheses) |
| Journal's citation record | 1 / 4 | Medical Hypotheses: journal h-index 138 (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 | 2004 — older than 20 years, still counted |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 757 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.5 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 4 / 6 | Cited 8.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 137 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Shaharyar M. Khan: h-index 20 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Virginia: institution h-index 1,118 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15193340) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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