Table 3.

Early-Onset Familial Alzheimer Disease (EOFAD)

Gene 1Proportion of EOFAD 2Age of Onset (yrs)Other
APP 10%-15%Usually 40s & 50s, occasionally 60s (range 30-65) 3
PSEN1 20%-70%Usually 40s or early 50s (range 30s-early 60s); onset after age 65 thought to be rare
  • Relatively rapid progression over 6-7 yrs is common.
  • Often associated w/seizures, myoclonus, & language deficits 4
  • Founder variants identified in residents of the state of Antioquia, Colombia 5 & in Caribbean Hispanics 6
PSEN2 ~5%40-75
  • Mean duration: 11 yrs
  • Reduced penetrance (i.e., asymptomatic heterozygotes age >80 yrs) reported 7
  • Founder variant identified in the Volga German population
Unknown20%-40% 8No major new gene for EOFAD has been identified because of overlap in the clinical presentation of AD and FTD caused by pathogenic variants in MAPT, GRN, C9orf72.

AD = Alzheimer disease; FTD = frontotemporal dementia

1.

Genes are in alphabetic order.

2.
3.
4.
5.
6.
7.
8.

It is likely that pathogenic variants in other genes causative of EOFAD will be identified because kindreds with autosomal dominant FAD with no known pathogenic variants in PSEN1, PSEN2, or APP have been described [Pasanen et al 2018].

From: Alzheimer Disease Overview

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