AI Article Synopsis

  • The study explores the genetics of cerebral amyloid angiopathy (CAA), which is not widely researched and can impact the understanding of Alzheimer's disease (AD).
  • Researchers conducted exome sequencing on 78 patients diagnosed with early-onset CAA, finding notable genetic variants, including pathogenic NOTCH3 mutations in two patients related to CADASIL, a rare vascular condition.
  • The findings suggest that there are shared genetic factors between AD and CAA beyond just the APOE gene, with potential susceptibility linked to other rare genetic variants in various risk factor genes.

Article Abstract

Introduction: Genetics of cerebral amyloid angiopathy (CAA) remains understudied.

Methods: We assessed variants in Alzheimer's disease (AD) risk factor genes and differential diagnosis genes by performing exome sequencing among 78 patients with early-onset definite or probable CAA, after negative screening for APP mutation or duplication.

Results: Among 14 genes involved in non-Aβ CAA, or vascular leukoencephalopathies, we detected pathogenic NOTCH3 variants in two patients, who exhibited lobar hematomas at the ages of 58 and 65, leading to a diagnosis redirection toward CADASIL. Of the remaining 76 patients, 23.1% carried at least one apolipoprotein E (APOE) ε2 allele and 43.6% carried at least one APOE ε4 allele, known as CAA risk factors. A total of 15 out of 76 (19.7%) carried either a loss-of-function or a rare predicted damaging missense or known AD risk variant in SORL1, TREM2, ABCA7, ABCA1, and ATP8B4.

Discussion: Exome sequencing allowed the redirection toward CADASIL in two patients and suggested shared genetic factors between AD and CAA, beyond the APOE gene.

Highlights: The genetic component of cerebral amyloid angiopathy (CAA) remains understudied.Rare differential diagnoses such as CADASIL should be considered, even in cases of cerebral hemorrhage.Our study suggests shared genetic factors between AD and CAA, beyond the gene.Rare variants in , and might be susceptibility factors in early-onset CAA.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585166PMC
http://dx.doi.org/10.1002/dad2.70027DOI Listing

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