Proposal for comparison between Dominant Inherit Alzheimer Disease and
sporadic early-onset Alzheimer?s disease.
 
   Lead Investigator:    Jorge Llibre-Guerra
   Institution      :    Dominantly Inherited Alzheimer's Network
   E-Mail           :    jllibre-guerra@wustl.edu
   Proposal ID      :    1521



   Proposal Description:
   Project Aim 1: To compare clinical presentation, neuropsychological performance and cognitive decline rate between DIAD and sporadic EOAD.    Project Aim 2: To examine the regional distribution of tau, amyloid-??, brain glucose metabolism, and structural atrophy, as well as their relationships, in DIAD and sporadic EOAD.    Project Aim 3: To determine CSF biomarkers levels and rate of change in DIAD and sEOAD.                                                                         Project Details:                                                                Alzheimer disease (AD) is the most common cause of dementia. By 2050, more than 131 million people will be affected[1]. Dementia is also the most costly illness in the United States with an estimated yearly expenditure between $157 billion and $215 billion[2].  Though generally considered a disease of the elderly, Alzheimer?s disease is also a leading cause of early age-of-onset dementia[5]. Patients who present with early-onset Alzheimer?s disease (EOAD) are defined in most studies as the onset of symptoms before age 65. Patients who develop sporadic Alzheimer's disease (AD) before age 65 (~5 of all AD patients) pose a clinical challenge and a scientific enigma. A significant number of patients presenting with EOAD will lack a significant family history of AD and no proven pathogenic mutation for AD (consider as sporadic EOAD).     Patients with ?sporadic? EOAD (sEOAD) are more likely to be carriers of the apolipoprotein E??4 allele (ApoE4), which is associated with early deposition of amyloid-#946 plaques [6]. In less than 1 of patients, EOAD is caused by dominant inherit (DIAD) mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes leading to early and rapid aggregation of amyloid-#946.    Overall, patients with EOAD show more rapid clinical decline and shorter survival than late-onset AD patients (LOAD) [7, 8]. At the same time, patients carrying DIAD mutati