Neuronal loss of the nucleus basalis of Meynert in primary progressive aphasia is associated with Alzheimer's disease neuropathological changes

Alzheimers Dement. 2022 Sep 28. doi: 10.1002/alz.12794. Online ahead of print.


Introduction: Imaging studies indicated basal forebrain reduction in primary progressive aphasia (PPA), which might be a candidate marker for cholinergic treatment. Nucleus basalis of Meynert (nbM) neuronal loss has been reported, but a systematic quantitative neuropathological assessment including the three clinical PPA variants is lacking.

Methods: Quantitative assessment of neuronal density and pathology was performed on nbM tissue of 47 cases: 15 PPA, constituting the different clinicopathological phenotypes, 14 Alzheimer's disease (AD), and 18 cognitively normals.

Results: Group-wise, reduced nbM neuronal density was restricted to AD. At the individual level, semantic variant PPA with underlying AD neuropathological change (ADNC) had lower neuronal densities, while those with frontotemporal lobar degeneration (FTLD) transactive response DNA binding protein 43 kDa (TDP-43) type C pathology were unaffected. Higher Braak stages and increased numbers of nbM-related pretangles were associated with nbM neuronal loss.

Discussion: nbM neuronal loss in PPA is related to ADNC. This study cautions against overinterpreting MRI-based basal forebrain volumes in non-AD PPA as neuronal loss.

Keywords: FTLD; basal forebrain; frontotemporal dementia; neuropathology; nucleus basalis of Meynert; pTDP-43; primary progressive aphasia; tau.