Current Alzheimer Research - Volume 13, Issue 1, 2016

Trisomy 21 and the consequent extra copy of the amyloid precursor protein (APP) gene and increased beta-amyloid (Aβ) peptide production underlie the universal development of Alzheimer’s disease (AD) pathology and high risk of AD dementia in people with Down syndrome (DS). Trisomy 21 and other forms of aneuploidy also arise among neurons and peripheral cells in both sporadic and familial AD and in mouse Read More

Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular patholo Read More

Down syndrome is an intellectual disability requiring periodic monitoring of cognition given the near universal presence of Alzheimer’s Disease related neuropathology and high rates of dementia in middle adulthood. We review current approaches to detecting decline in this population, including informant-based measures, dementia screening tools, and neuroimaging techniques. The challenges for detecting decline in th Read More

Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expecta Read More

It is well established that individuals with Down syndrome develop Alzheimer’s disease neuropathology by middle age. Both in Alzheimer’s disease and Down syndrome, this is accompanied by the atrophy of NGF-dependent cholinergic neurons of the basal forebrain. An NGF trophic compromise in Alzheimer’s disease had been early suspected. This hypothesis was discarded with the finding of unaltered NGF mRNA synthesis and o Read More

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer’s disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regi Read More

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of Read More

Although Down syndrome (DS) can be diagnosed prenatally, currently there are no effective treatments to lessen the intellectual disability (ID) which is a hallmark of this disorder. Furthermore, starting as early as the third decade of life, DS individuals exhibit the neuropathological hallmarks of Alzheimer’s disease (AD) with subsequent dementia, adding substantial emotional and financial burden to their families and society at Read More