A Study of Amyloid-β and Phosphotau in Plaques and Neurons in the Hippocampus of Alzheimer’s Disease Patients

The main pathological hallmarks in Alzheimer’s disease (AD) are the presence of extracellular amyloid plaques, primarily consisting of amyloid-β (Aβ) peptide, and the accumulation of paired helical filaments of hyperphosphorylated tau protein (PHF(-Tau)) within neurons. Since CA1 is one of the most affected regions in AD, mainly at early stages, we have performed a detailed analysis of the CA1 region from 11 AD patients (demented and clinically similar; Braak stages IV-VI) to better understand the possible relationship between the presence and distribution of different neurochemical types of Aβ plaques and PHF(-Tau) immunoreactive ( (- ir) ) neurons. Hence, we have examined hippocampal sections in confocal microscopy images from double and triple-immunostained sections, to study labeled plaques and PHF(-Tau-ir) neurons using specific software tools. There are four main findings in the present study. First, the pyramidal layer of proximal CA1 (close to CA2) contains the smallest number of both plaques and PHF(-Tau-ir) neurons. Second, a large proportion of Aβ(-ir) plaques were also characterized by the presence of PHF(-Tau-ir). Third, all plaques containing one of the two PHF(-Tau) isoforms also express the other isoform, that is, if a plaque contains PHF(pS396), it also contains PHF(AT8), and vice versa. Fourth, the coexpression study of both PHF(-Tau) isoforms in CA1 neurons revealed that most of the labeled neurons express only PHF(pS396). Our findings further support the idea that AD is not a unique entity even within the same neuropathological stage, since the microanatomical/neurochemical changes that occur in the hippocampus greatly vary from one patient to another.