Alzheimer’s Disease

Description

  • Alzheimer’s disease (AD) is a typically adult-onset, progressive neurodegenerative condition characterized by dementia. AD-associated dementia typically starts with subtle but progressive memory failure. Other common findings include: confusion, poor judgment, language disturbance, visual complaints, agitation, withdrawal and hallucinations. Approximately 95% of all AD has later onset of >60-65 years, whereas 5% of the condition is early onset (age 60-65 years).
  • A diagnosis of AD is typically made using clinical and neuropathologic assessment.
  • Approximately 25% of all AD is consider familial (>= 3 members of the same family with AD).
  • Late-onset AD is thought to be a complex disorder that may involve multiple susceptibility genes (including the APOE e4 allele).
  • Early-onset AD is associated with a few known causative genes including: APP, PSEN1, PSEN2.
  • For AD, genetic testing is recommended for all patients with a strong family history (>= 3 persons affected in the family total), or young age of onset (< 60 years).

How often is a hereditary cause identified?

  • Studies in patients with early-onset AD have reported genetic testing yields of 5-13% when analyzing three main associated genes: APP, PSEN1 and PSEN2.

How does identifying a hereditary cause change a patient’s medical management?

  • Therapies are under development to target specific genetic causes of AD.
  • If a genetic cause is identified, this can provide information for family planning as well as information to understand the risk to family members.

How are these conditions inherited?

  • Early-onset Alzheimer’s Disease which is known to be cause by a pathogenic variant in one of the known AD-associated genes is typically inherited in an autosomal dominant pattern.
  • In families with >= 3 persons in a family with AD, and no known causative gene, inheritance is thought to be multi-factorial and potentially involved multiple susceptibility genes.

Where can I learn more about AD?

References

  • Dratch L, Azage M, Baldwin A, Johnson K, Paul RA, Bardakjian TM, Michon SC, Amado DA, Baer M, Deik AF, Elman LB, Gonzalez-Alegre P, Guo MH, Hamedani AG, Irwin DJ, Lasker A, Orthmann-Murphy J, Quinn C, Tropea TF, Scherer SS, Ellis CA. Genetic testing in adults with neurologic disorders: indications, approach, and clinical impacts. J Neurol. 2023 Oct 27. doi: 10.1007/s00415-023-12058-6. Epub ahead of print. PMID: 37891417.
  • Bird TD. Alzheimer Disease Overview. 1998 Oct 23 [Updated 2018 Dec 20]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1161/
  • Nudelman KNH, Jackson T, Rumbaugh M, Eloyan A, Abreu M, Dage JL, Snoddy C, Faber KM, Foroud T, Hammers DB; DIAN/DIAN-TU Clinical/Genetics Committee; Taurone A, Thangarajah M, Aisen P, Beckett L, Kramer J, Koeppe R, Kukull WA, Murray ME, Toga AW, Vemuri P, Atri A, Day GS, Duara R, Graff-Radford NR, Honig LS, Jones DT, Masdeu JC, Mendez M, Musiek E, Onyike CU, Riddle M, Rogalski E, Salloway S, Sha SJ, Turner RS, Wingo TS, Wolk DA, Carrillo MC, Dickerson BC, Rabinovici GD, Apostolova LG; LEADS Consortium. Pathogenic variants in the Longitudinal Early-onset Alzheimer's Disease Study cohort. Alzheimers Dement. 2023 Nov;19 Suppl 9(Suppl 9):S64-S73. doi: 10.1002/alz.13482. Epub 2023 Oct 6. PMID: 37801072; PMCID: PMC10783439.