Current Genetic Medicine Reports

, Volume 8, Issue 1, pp 1–16 | Cite as

Alzheimer’s Disease Genetics: Review of Novel Loci Associated with Disease

  • Miguel Tábuas-Pereira
  • Isabel Santana
  • Rita GuerreiroEmail author
  • José Brás
Neurogenetics and Psychiatric Genetics (C Cruchaga and C Karch, Section Editors)
Part of the following topical collections:
  1. Neurogenetics and Psychiatric Genetics


Purpose of the Review

The amyloid cascade hypothesis has shaped the Alzheimer’s disease (AD) research field for the last 30 years. Originally hinged on mutations in the APP pathway, its linearity has become limited to explain all the disease subtypes and features. The understanding of the disease has evolved significantly, now being viewed as a polygenic disease, with more and more risk genes uncovered by several approaches, namely, by genome-wide association studies. Here we reviewed the literature for the latest loci reported to be associated with Alzheimer’s disease using genome-wide association studies and discussed the possible involvement of specific genes located at these loci, in the disease.

Recent Findings

The largest genome-wide association studies for AD have been published in the last year, adding more loci of interest: ADAM10, ADAMTS1, ADAMTS4, ACE/PSMC5, APH1B, WWOX/MAF, HESX1, HS3ST1/CLNK, ANKRD31, CNTNAP2, NDUFAF6, ECHDC3, SPPL2A, KAT8/BCKDK, IQCK, SCIMP, BRZAP-1/BZRAP1-AS1, ALPK2, BHMG1.


The definite association with AD for some of the reported genes needs further evidence. Regardless, the implicated genes add support for the involvement of several pathways, such as lipids homeostasis and immune pathways. These also point to synaptic dysfunction and cell-cycle dysregulation as mechanisms involved in the disease, extending the understanding of Alzheimer’s disease pathophysiology.


Alzheimer’s disease Dementia Genome-wide association studies GWAS Genetics Pathways 


Compliance with ethical standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

40142_2020_182_MOESM1_ESM.docx (108 kb)
ESM 1 (DOCX 108 kb)


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of NeurologyCentro Hospitalar e Universitário de CoimbraCoimbraPortugal
  2. 2.Faculty of MedicineUniversidade de CoimbraCoimbraPortugal
  3. 3.Center for Neurodegenerative ScienceVan Andel InstituteGrand RapidsUSA
  4. 4.Division of Psychiatry and Behavioral MedicineMichigan State University College of Human MedicineGrand RapidsUSA

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