Linkage analysis of multiplex Caribbean Hispanic families loaded for unexplained early-onset cases identifies novel Alzheimer's disease loci

Rong Cheng, Min Tang, Izri Martinez, Temitope Ayodele, Penelope Baez, Dolly Reyes-Dumeyer, Rafael Lantigua, Martin Medrano, Ivonne Jimenez-Velazquez, Joseph H. Lee, Gary W. Beecham, Christiane Reitz

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Introduction: Less than 10% of early-onset Alzheimer's disease (EOAD) is explained by known mutations. Methods: We conducted genetic linkage analysis of 68 well-phenotyped Caribbean Hispanic families without clear inheritance patterns or mutations in APP, PSEN1, and PSEN2 and with two or more individuals with EOAD. Results: We identified 16 (logarithm of odds > 3.6) linked regions, including eight novel loci for EOAD (2p15, 5q14.1, 11p15.1, 13q21.22, 13q33.1, 16p12.1, 20p12.1, and 20q11.21) and eight regions previously associated with late-onset Alzheimer's disease. The strongest signal was observed at 16p12.1 (25 cM, 33 Mb; heterogeneity logarithm of odds = 5.3), ∼3 Mb upstream of the ceroid lipofuscinosis 3 (CLN3) gene associated with juvenile neuronal ceroid lipofuscinosis (JNCL), which functions in retromer trafficking and has been reported to alter intracellular processing of the amyloid precursor protein. Discussion: This study supports the notion that the genetic architectures of unexplained EOAD and late-onset AD overlap partially, but not fully.

Original languageEnglish (US)
Pages (from-to)554-562
Number of pages9
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume10
DOIs
StatePublished - Jan 1 2018

Keywords

  • Early-onset Alzheimer's disease
  • Genetics
  • Linkage analysis
  • Linkage loci
  • Non-Mendelian

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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