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• W2895945021 abstract "The basal forebrain cholinergic neurons are highly vulnerable to neurofibrillary degeneration in typical amnestic forms of Alzheimer disease (AD). However, little is known of the vulnerability of these neurons in the atypical form of AD that causes primary progressive aphasia (PPA). PPA is a clinical syndrome characterized by progressive language impairment, caused by either underlying AD pathology, Frontotemporal Lobar Degeneration (FTLD) with 43kDa transactive response DNA-binding protein proteinopathy (FTLD-TDP), or FTLD-tau, with accumulation of abnormally phosphorylated tau. This study aimed to evaluate the vulnerability of the cholinergic basal forebrain in PPA, comparing PPA-AD and PPA-TDP. A semiquantitative analysis was conducted in the brains of 10 participants, aged 66 years ± 7.3, who were clinically diagnosed with PPA. Five cases had confirmed Alzheimer pathology (PPA-AD) and 5 FTLD-TDP (PPA-TDP) pathology. A series of 1 in 24 40um-thick whole-hemisphere brain sections were stained with Thioflavin-S to visualize neurofibrillary tangles (NFT) in PPA-AD, and immunohistochemically stained using an antibody against TDP-43 to visualize inclusions in PPA-TDP. All sections were histologically processed with cresyl violet Nissl stain to visualize neurons. Severity of NFT pathology and TDP-43 inclusions were assessed in the basal forebrain. NFT pathology was quantified using Thioflavin-S fluorescence, TDP-43 pathology was quantified using TDP-43 immunoreactivity, and the total neuronal population of the basal forebrain was determined in Nissl-stained sections. NFT pathology was more substantial in magnocellular basal forebrain cholinergic neurons in PPA-AD. Moreover, significant cholinergic neuron loss was observed. These results are consistent with the pattern of basal forebrain pathology observed in amnestic AD. In contrast, we found minimal TDP pathology in PPA-TDP (<1% of magnocellular cholinergic neurons), with only pre-inclusions and a virtual absence of mature TDP inclusions, suggesting a relative sparing of the basal forebrain in PPA-TDP. The basal forebrain is highly vulnerable in PPA-AD, accumulating NFT pathology and displaying neuronal loss consistent with pathology and degeneration observed in amnestic AD. However, the basal forebrain shows low vulnerability to TDP-43 inclusions, suggesting a greater vulnerability of basal forebrain cholinergic neurons to Alzheimer type tau pathology." @default.
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• W2895945021 date "2018-07-01" @default.
• W2895945021 modified "2023-10-16" @default.
• W2895945021 title "P3‐460: VULNERABILITY OF THE CHOLINERGIC BASAL FOREBRAIN TO AD VERSUS FTLD‐TDP PATHOLOGY IN PRIMARY PROGRESSIVE APHASIA" @default.
• W2895945021 doi "https://doi.org/10.1016/j.jalz.2018.06.1824" @default.
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