role of tau in the pathology of Alzheimer disease

Introduction

Carriers of the autosomal dominant PSEN2 gene mutation are genetically destined to develop symptomatic Alzheimer's disease by 52 years of age. Jorge J. Llibre-Guerra, M. Victoria Fernandez, Nelly Joseph-Mathurin and many other DIAN investigators describe in a case report an exceptional resilience mutation carrier, an individual with a p.Asn141Ile PSEN2 gene mutation, surviving to his mid 70's without significant neurofibrillary tangles* or cognitive impairment. His brain was full of amyloid plaques. This case report provides strong supporting evidence that PHF-tau & neurofibrillary tangles define Alzheimer pathology as described by Braak & Braak in 1991. (see histopathology of Alzheimer's disease). Beta-Amyloid is insufficient to cause symptoms of Alzheimer's disease.

* Neurofibrillary tangles in the exceptional resilience carrier were confined to the occipital cortex

# The PSEN2 gene mutation [1q31-q42] of familial Alzheimer's disease-4 (FAD-4) is a point mutation p.Asn141Ile resulting in ~1.2-3 fold increase in production of A-beta 42.

This case report did not identify any previously described protective factors present in the genome of the exceptional resilience mutation carrier, but putative protective variants are described. The DIAN investigators have established a platform at the Dominantly Inherited Alzheimer Network (DIAN) for interested investigators to access the data, propose studies & suggest collaboration ideas aimed at understanding how this individual has resisted the clinical onset of Alzheimer's disease.

More general terms

• histopathology of Alzheimer's disease