Alzheimer's disease-related plaques in nondemented subjects

Alzheimer's disease (AD) pathology was assessed in 587 nondemented subjects, with age at death at or more than 50 years. In 307 subjects, amyloid-β (Aβ) immunoreactive (IR) plaques were seen; in 192 subjects, neuritic plaques (NPs) stained with modified Bielschowsky silver stain (mBky) were observed. In 20% of the whole cohort and in 62% of the 192 subjects with NPs in mBky, hyperphosphorylated tau (HPtau) IR NPs were seen. In most cases in this nondemented cohort, the HPtau IR NPs were observed either sparsely or to a moderate extent. The correlation between the NP score and Braak stage was best (r=0.6, P<.001) when HPtau immunohistochemistry was used. Eighty-three percent of the subjects could not be categorized following the 1997 National Institute on Aging and the Reagan Institute (NIA-RI) recommendations, whereas the 2012 National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines were applicable for all study subjects. Twenty-eight subjects had an intermediate level of AD neuropathological change according to the 2012 NIA-AA guidelines, and 25 of these 28 subjects displayed HPtau IR NPs in the temporal cortex. It is noteworthy, however, that as many as 119 out of the 192 subjects with NPs in mBky displayed HPtau IR NPs in the temporal cortex. Ninety-four of these 119 subjects with neocortical HPtau IR NPs had a low level of neuropathological AD change according to the 2012 NIA-AA guidelines because they were in Braak stages I and II. Thus, 94 subjects were not acknowledged as being at risk for AD when applying the 2012 NIA-AA guidelines. We suggest that to identify all subjects with cortical HPtau pathology and, consequently, probably being at risk for developing AD, in addition to the level of AD neuropathological change as recommended by the 2012 NIA-AA guidelines, assessment of HPtau IR NPs in the neocortex should be carried out.