Lack of continuum between cerebral aging and Alzheimer's disease as revealed by PHF-tau and A beta biochemistry

Alzheimer's disease (AD) is characterized by two types of cortical brain le sions: senile plaques and neurofibrillary tangles. The same lesions are fou nd, in moderate quantities, during 'normal' cerebral aging, is there then a continuum between normal aging and AD? Answers could come from the study o f the spatiotemporal distribution of brain lesions in a large population co mprising non-demented cases and AD patients at different stages of the illn ess. Within the current investigation, we present the results from our stud y of 120 subjects, including 60 non-demented aged cases prospectively studi ed. The biochemical and immunohistochemical mapping of paired helical filam ent (PHF)-tau and A beta peptide, basic components of neurofibrillary degen eration (NFD) and senile plaques respectively, was performed in many cortic al brain areas. We found that NFD affected all cases older than 75 years of age. PHF-tau was always observed initially in the hippocampal region, some times in low amounts, even in nonagenerians. NFD extent in other brain area s was stereotyped and hierarchical. This progression was divided into 10 st ages, according to the 10 brain regions successively affected. NFD was ofte n asymptomatic before stage 6 (Brodmann areas 35, 28, 34, 38, 21, 20 affect ed progressively). Our data do not support the continuum hypothesis between aging and AD as we observed two distinct populations: one corresponding to normal aging, with NFD and no amyloid deposits, and the other correspondin g to the different stages of AD, with both lesions present. These data enab led us to determine the Criteria to Establish a Biochemical (post-mortem) D iagnosis of AD (CEBDAD).