Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: A quantitative analysis across subregions of the basal forebrain

Elliott J. Mufson, Mark Bothwell, Jeffrey H. Kordower

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

Magnocelular neurons comprising the Ch1-Ch4 regions of the basal forebrain provide topographic cholinergic innervation to the cerebral cortex, thalamus, and basolateral nucleus of the amygdala. Most quantitative studies analyzing the status of these neurons in Alzheimer's disease (AD) have employed Nissl-stained preparations. These studies principally analyzed large neurons of a prespecified cell diameter. Since basal forebrain neurons atrophy in Alzheimer's disease, an immunocytochemical marker for these neurons would appear to be a better alternative for determining whether there is regionally specific degeneration of cholinergic neurons across subregions of the basal forebrain. Brain sections from seven AD and five agedmatched control patients were immunocytochemically stained with a monoclonal antibody raised against the receptor for nerve growth factor (NGF), a probe which has previously been demonstrated to extensively and exclusively colocalize with cholinergic basal forebrain neurons in humans (17, 25, 35). NGF receptor0immunoreactive neurons within the hippocampal projecting nuclei of the medial septum (Ch1) and vertical limb of the diagonal band (Ch2) were minimally affected in AD as compared to control cases. In Contrast, the Ch4 region demonstrated a significant loss of NGF receptor-immunoreactive neurons in AD that inversely correlated (-0.786) with the duration of the disease process. All four subregions of Ch4 were affected in the AD cases with the anterolateral (76.4%), intermediate (62.1%) and posterior divisions (76.5%) demonstrating the greatest reduction in NGF receptor-immunoreactive neurons. Nissl-counterstained sections failed to reveal magnocellular neurons which were not immunoreactive for the NGF receptor, suggesting that reductions in immunocytochemically stained neurons reflects neuron loss and not the failure of viable neurons to synthesize NGF receptors. These data indicate that cholinergic basal forebrain neurons which project to the amygdala, as well as to the temporal, frontobasal, and frontodorsal cortices, are most affected in AD.

Original languageEnglish (US)
Pages (from-to)221-232
Number of pages12
JournalExperimental Neurology
Volume105
Issue number3
DOIs
StatePublished - Sep 1989
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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