GRK5 Deficiency Leads to Selective Basal Forebrain Cholinergic Neuronal Vulnerability.


Journal Article

Why certain diseases primarily affect one specific neuronal subtype rather than another is a puzzle whose solution underlies the development of specific therapies. Selective basal forebrain cholinergic (BFC) neurodegeneration participates in cognitive impairment in Alzheimer's disease (AD), yet the underlying mechanism remains elusive. Here, we report the first recapitulation of the selective BFC neuronal loss that is typical of human AD in a mouse model termed GAP. We created GAP mice by crossing Tg2576 mice that over-express the Swedish mutant human β-amyloid precursor protein gene with G protein-coupled receptor kinase-5 (GRK5) knockout mice. This doubly defective mouse displayed significant BFC neuronal loss at 18 months of age, which was not observed in either of the singly defective parent strains or in the wild type. Along with other supporting evidence, we propose that GRK5 deficiency selectively renders BFC neurons more vulnerable to degeneration.

Full Text

Cited Authors

  • He, M; Singh, P; Cheng, S; Zhang, Q; Peng, W; Ding, X; Li, L; Liu, J; Premont, RT; Morgan, D; Burns, JM; Swerdlow, RH; Suo, WZ

Published Date

  • May 19, 2016

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 26116 -

PubMed ID

  • 27193825

Pubmed Central ID

  • 27193825

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

International Standard Serial Number (ISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep26116


  • eng