Alzheimer's Disease: An Updated Overview of Its Genetics.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing genetic associations in Alzheimer's disease without systematic search or meta-analytic methodology
PubMed 36835161 · doi:10.3390/ijms24043754
What was done
This narrative review synthesizes current literature on the genetic basis of Alzheimer's disease (AD). The authors describe the distinction between early-onset familial AD and late-onset sporadic AD (LOAD), reviewing mutations in amyloid precursor protein pathways and polymorphisms identified through genome-wide association studies (GWAS) across various neuropathological mechanisms.
What was found
Familial early-onset AD (<65 years) constitutes 1-5% of total cases and is linked to mutations in PSEN1, PSEN2, or APP. Sporadic late-onset AD (>65 years) accounts for 95% of cases, with aging identified as the primary risk factor alongside polygenic loci associated with amyloid-beta and tau processing, synaptic/mitochondrial dysfunction, neurovascular alterations, oxidative stress, and neuroinflammation. No numerical effect sizes or odds ratios are reported in the abstract.
Why it matters
Understanding the distinct genetic architectures of familial and sporadic Alzheimer's disease helps clarify disease mechanisms and supports the identification of risk biomarkers and therapeutic targets.
Limits
As a narrative review, the paper presents no original patient data, cohort analyses, or systematic search methodology. The abstract reports no quantitative risk estimates or effect sizes for the GWAS-identified polymorphisms.
Cited by
- context The majority of dementia cases stem from mitochondrial dysfunction rather than rare inherited genetic mutations.