Multidimensional evaluation in clinical diagnosis of Alzheimer’s disease: genetic risk in Alzheimer’s disease and neurodegenerative dementias

Background Late onset degenerative dementia is a growing, common and complex disorder in which the aetiological role played by environment and genes has not yet been established. A familial component is frequently ascertained in Alzheimer’s disease (AD) (30% of first degree relatives affected) and also in Frontotemporal Dementia (FTD) (40-60%). Early onset degenerative dementia has sometimes been recognized as caused by autosomal dominant genes, Presenilines (PS1 and PS2) and the Amyloid Precursor Protein (APP) in AD, whereas in Frontotemporal dementia, two major genes (Microtubule Associated Protein tau, MAPT and Progranulin, PGRN) have also been identified. PS1 and MAPT mutations have been identified also in in very early onset patients (PS1 24 years [1], MAPT 22 years [2]), but also in late onset patients (PS1 78 years [3], MAPT 75 years [4] 87 years [5]. To evaluate whether FAD and PGRN gene mutations account for late onset dementia.