Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer's disease

Scott E. Counts, Er Yun Chen, Shaoli Che, Milos D. Ikonomovic, Joanne Wuu, Stephen D. Ginsberg, Steven T. DeKosky, Elliott J. Mufson

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Galanin (GAL)-containing fibers enlarge and hyperinnervate remaining cholinergic basal forebrain (CBF) neurons within the anterior nucleus basalis (NB) in late-stage Alzheimer's disease (AD). Whether GAL hypertrophy occurs in the CBF in the prodromal or early stages of AD remains unknown. The present study used GAL immunohistochemistry and an unbiased semiquantitative scoring method to evaluate GAL innervation in the anterior NB of subjects clinically diagnosed as having no cognitive impairment, mild cognitive impairment or early-stage (mild/moderate) AD. There was no difference in GAL fiber staining within the anterior NB across the three clinical groups examined. Furthermore, GAL fiber innervation was not correlated with the number of NB neurons expressing the nerve growth factor receptors p75NTR or TrkA or with cortical choline acetyltransferase activity in the same cases. Single-cell gene expression analysis demonstrated that cholinergic NB neurons express mRNA for the GAL receptors GALR1, GALR2 and GALR3, yet the levels of these mRNAs were unchanged across the three diagnostic groups. These observations indicate that GAL hypertrophy within the anterior NB subfield is a late-stage AD response, which may play a role in regulating the cholinergic tone of remaining basocortical projection neurons.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalDementia and Geriatric Cognitive Disorders
Volume21
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Basal forebrain hyperinnervation
  • Galanin hypertrophy

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Geriatrics and Gerontology

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