Murray, Melissa E.

AbstractMutations in microtubule‐associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP‐17). Here, we describe a patient with FTDP‐17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40‐year‐old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP‐17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP‐17 due to p.E372G were similar to those of p.G389R, including tau‐immunoreactive Pick body‐like neuronal inclusions and swollen, tapering thread‐like processes in white matter immunoreactive for 3‐repeat and 4‐repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP‐17 similar to p.G389R.

AbstractIntroductionCerebrovascular lesions on MRI are common in Alzheimer's disease (AD) dementia, but less is known about their frequency and impact on dementia with Lewy bodies (DLB).MethodsWhite‐matter hyperintensities (WMHs) and infarcts on MRI were assessed in consecutive DLB (n = 81) and AD dementia (n = 240) patients and compared to age‐matched and sex‐matched cognitively normal subjects (CN) from a population‐based cohort.ResultsDLB had higher WMH volume compared to CN, and WMH volume was higher in the occipital and posterior periventricular regions in DLB compared to AD. Higher WMH volume was associated with history of cardiovascular disease and diabetes but not with clinical disease severity in DLB. Frequency of infarcts in DLB was not different from CN and AD dementia.DiscussionIn DLB, WMH volume is higher than AD and CN and appears to be primarily associated with history of vascular disease.