Deposition of tau in the brain in Alzheimer's disease is related to the amount of Aβ40 but not Aβ42(43) deposits and the presence of apolipoprotein E ε4 allele

Abstract

Introduction: Alzheimer's disease (AD) is characterized by the widespread deposition of amyloid β protein (Aβ) in the form of extracellular plaques and the intracellular accumulation of pathological aggregates of the microtubule associated protein, tau, in the form of neurofibrillary tangles and neuropil threads. We have investigated relationships between the amount of plaque amyloid and tau deposition in brain in sporadic AD and the affect of apolipoprotein E (APOE) genotype on tau load.Material and methods: Wax sections of frontal cortex from 109 cases of late onset AD were immunostained using AT8 antibody to detect deposition of pathological tau proteins. The amount of tau, and Aβ as Aβ40 and Aβ42(43), was quantified by image analysis. The APOE genotype was determined by standard methods.Results: The amount of tau within frontal cortex correlated inversely with patient age but not duration of illness suggesting a more aggressive ‘spread’ of disease into frontal lobes by time of death in younger patients. Tau load correlated (P < 0.001) with Aβ40 but not Aβ42(43) levels, and was also greater in patients with APOE ε4 allele than those without, increasing in line with ε4 allele copy number.Conclusions: Results suggest that tau deposition in late onset AD is favoured in the presence of APOE ε4 allele and when Aβ40 levels are high, the latter also being associated with ε4 allele. Aβ40 is preferentially present in cored plaques where microglial cells are frequent. The amount of tau deposited in the brain in AD may therefore reflect the extent of local neuroinflammatory changes.