title: Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer's disease.
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 p75(NTR) 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.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Counts
authors.forename: Er-Yun
authors.initials: EY
authors.lastname: Chen
authors.forename: Shaoli
authors.initials: S
authors.lastname: Che
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.forename: Joanne
authors.initials: J
authors.lastname: Wuu
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Ginsberg
authors.forename: Steven T
authors.initials: ST
authors.lastname: Dekosky
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism; D020532:Basal Nucleus of Meynert / Q000378:metabolism* / Q000473:pathology*; D018929:Cell Culture Techniques; D002799:Cholinergic Fibers / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D019004:Galanin / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D044091:Receptor, Galanin, Type 1 / Q000235:genetics; D044092:Receptor, Galanin, Type 2 / Q000235:genetics; D044093:Receptor, Galanin, Type 3 / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; D019004:Galanin