Systematic Review · e0006
Lipid metabolism in Alzheimer disease: a systematic review of genome-wide association studies
Zulfiya Kachiyeva, Arshyn Tlenshieva, Zhanerke Tileules, Almas Kauysbekov, Dinara Turarova. Lipid metabolism in Alzheimer disease: a systematic review of genome-wide association studies. Global Medical Reviews. 2026;1(2):5–13.
Abstract
Background
Alzheimer disease is a polygenic disorder involving lipid transport, cholesterol homeostasis and microglial biology. This review aimed to synthesize genome-wide association study evidence on lipid-metabolism pathways and distinguish replicated associations from mechanistic hypotheses.
Methods
Searches of PubMed/MEDLINE, Scopus and Web of Science were run from inception through February 2026. Selection followed the eligibility criteria described in the Methods within a PRISMA 2020-informed structure. Risk of bias and certainty were not formally assessed. Findings were synthesized narratively, because cohorts, phenotypes, analytic pipelines and pathway definitions differed substantially.
Results
Fifty-two studies met the eligibility criteria, and five large association studies are summarized in Table 2 as the principal evidence base. Recurrent signals involved APOE, ABCA7, CLU, BIN1, PICALM, TREM2, CR1 and SORL1. Lipid transport and efflux, cholesterol and phospholipid homeostasis, endosomal trafficking and microglial immune signaling formed interconnected biological themes. Many associated variants were non-coding, and evidence for causality was uneven.
Conclusions
Genetic association evidence supports a relationship between lipid regulation and Alzheimer disease susceptibility, but does not establish causal genes or therapeutic efficacy. Functional validation and multi-ancestry studies are required before translation into individualized risk prediction or treatment.
Keywords
Article history
- Received
- Revised
- Accepted
- Scheduled online publication
Peer-review model: Double-blind external peer review · Version: Version of Record
Supplementary materials
Supplementary tables and materials are included within the Version of Record PDF and HTML full text where present.