Increased aggression in males in transgenic Tg2576 mouse model of Alzheimer's disease.

Behavioural and psychological signs and symptoms of dementia encompass a wide range of neuropsychiatric disturbances which coincide with progressing cognitive decline in Alzheimer's disease (AD). Physical aggression and agitation, which occurs in 20-65% of AD patients, is physically and emotionally stressful, not only to patients but also to immediate family and caregivers. The exact mechanisms underlying the increased aggressive behaviour in AD has yet to be elucidated.

Genome-wide analysis of genetic loci associated with Alzheimer disease.

Context: Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD).

Objectives: To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35,000 persons (8371 AD cases).

Design, Setting, And Participants: In stage 1, we identified strong genetic associations (P < 10(-3)) in a sample of 3006 AD cases and 14,642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS.

Altered amyloid-beta metabolism and deposition in genomic-based beta-secretase transgenic mice.

Amyloid-beta (Abeta) the primary component of the senile plaques found in Alzheimer's disease (AD) is generated by the rate-limiting cleavage of amyloid precursor protein (APP) by beta-secretase followed by gamma-secretase cleavage. Identification of the primary beta-secretase gene, BACE1, provides a unique opportunity to examine the role this unique aspartyl protease plays in altering Abeta metabolism and deposition that occurs in AD. The current experiments seek to examine how modulating beta-secretase expression and activity alters APP processing and Abeta metabolism in vivo.

Hereditary cerebral hemorrhage with amyloidosis Dutch type (AbetaPP 693): decreased plasma amyloid-beta 42 concentration.

Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) is a rare autosomal dominant disorder caused by an amyloid-beta precursor protein (AbetaPP) 693 mutation that clinically leads to recurrent hemorrhagic strokes and dementia. The disease is pathologically characterised by the deposition of Abeta in cerebral blood vessels and as plaques in the brain parenchyma. This study measured the Abeta40 and Abeta42 concentration in plasma of Dutch AbetaPP693 mutation carriers and controls.