title: Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome.
abstract: Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal forebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons has been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain. The present study examined the interrelationship between reductions in CBF/trkA-containing neurons and the overexpression of galaninergic fibers within the nucleus basalis in DS. Within the nucleus basalis stereologic evaluation revealed a 46% reduction in the number of trkA-immunopositive neurons, whereas optical density measurements displayed a nonsignificant 18% reduction in neuronal trkA immunoreactivity in DS as compared with age-matched controls. Western blot analysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleus basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant reduction in trkA within the nucleus basalis and cortex with only a moderate hypertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD basal forebrain.
authors.affiliation: Department of Neurological Sciences and Rush Alzheimer's Disease Center, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Sendera
authors.forename: S Y
authors.initials: SY
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Jaffar
authors.forename: P B
authors.initials: PB
authors.lastname: Kozlowski
authors.forename: J H
authors.initials: JH
authors.lastname: Kordower
authors.forename: Y
authors.initials: Y
authors.lastname: Mawal
authors.forename: H U
authors.initials: HU
authors.lastname: Saragovi
authors.forename: E J
authors.initials: EJ
authors.lastname: Mufson
mesh_terms: D000368:Aged; D020532:Basal Nucleus of Meynert / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019004:Galanin / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*; D012016:Reference Values
chemical_list: D020800:Receptor, Nerve Growth Factor; D019004:Galanin; D020917:Receptor, trkA