Clinical and biomarker investigation of a patient with a novel presenilin-1 mutation (A431V) in the mild cognitive impairment stage of Alzheimer’s Disease

Abstract We report an individual who developed Alzheimer’s disease (AD) due to a novel presenilin-1 mutation (Alanine→Valine at codon 431). When he first presented, the patient met criteria for mild cognitive impairment but progressed over 16 months to fulfill diagnostic criteria of AD. At his first presentation, he showed widespread metabolic deficits in the posterior cingulate, lateral parietal, posterior parietal, and medial temporal regions on positron emission tomography as well as elevated tau and phospho-tau levels in cerebrospinal fluid (CSF). We suggest that functional neuroimaging and CSF biomarkers can serve as useful predictors of development of AD. Accumulation of pathologic tau isoforms and neuron death occur even in the mildest clinical stages of AD.