Nerve growth factor receptor expressing human basal forebrain neurons: pathologic alterations in Alzheimer's and...

Normal aged human basal forebrain tissue immunohistochemically stained with a monoclonal antibody for nerve growth factor receptor (NGFR) revealed a continuum of NGFR containing neurons in brain regions corresponding to Ch1-Ch4. NGFR immunoreactive neurons were observed within the medial septum (Ch1), vertical (Ch2) and horizontal (Ch3) limb nuclei of the diagonal band and nucleus basalis (Ch4) complex. Occasional dystrophic NGFR containing neurons were observed within the Ch subfields. Colocalization experiments demonstrated that virtually all (95%) NGFR containing perikarya stained positively for the specific cholinergic marker acetylcholinesterase. On the other hand, occasional cholinergic negative NGFR positive neurons were seen in the putamen of the striatal complex. In Alzheimer's disease, subfields of the basal forebrain revealed extensive neuronal loss and shrinkage, dystrophic fibers as well as normal appearing neurons. Each AD case exhibited an individual pattern of cell loss. Within the Ch1-4 subfields NGFR and ChAT colocalized, indicating that the NGFR remained coupled to cholinergic neurons in AD. In some Parkinson's cases there was a severe loss of NGFR containing basal forebrain neurons. These findings indicate that NGFR containing basal forebrain neurons colocalize with ChAT, are severely affected in AD, in some PD cases, and NGFR remains coupled to cholinergic perikarya in both neurodegenerative disorders.