Details

Autor(en) / Beteiligte

• Hoogmartens, Julie
• Cacace, Rita
• Van Broeckhoven, Christine

Titel

Insight into the genetic etiology of Alzheimer's disease: A comprehensive review of the role of rare variants

Ist Teil von

• Alzheimer's & dementia : diagnosis, assessment & disease monitoring, 2021, Vol.13 (1), p.e12155-n/a

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Early‐onset Alzheimer's disease (EOAD) is generally known as a dominant disease due to highly penetrant pathogenic mutations in the amyloid precursor protein, presenilin 1 and 2. However, they explain only a fraction of EOAD patients (5% to 10%). Furthermore, only 10% to 15% of EOAD families present with clear autosomal dominant inheritance. Studies showed that only 35% to 60% of EOAD patients have at least one affected first‐degree relative. Parent–offspring concordance in EOAD was estimated to be <10%, indicating that full penetrant dominant alleles are not the sole players in EOAD. We aim to summarize current knowledge of rare variants underlying familial and seemingly sporadic Alzheimer's disease (AD) patients. Genetic findings indicate that in addition to the amyloid beta pathway, other pathways are of importance in AD pathophysiology. We discuss the difficulties in interpreting the influence of rare variants on disease onset and we underline the value of carefully selected ethnicity‐matched cohorts in AD genetic research.