Amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer disease, and the accumulation of APP products ultimately leads to the familiar histopathological and clinical manifestations associated with this most common form of dementia.
A novel APP mutation (E693Δ) that produced a variant Aβ lacking glutamate 22 (E22Δ) in Japanese pedigrees was recently identified to have AD-type dementia without amyloid plaque formation but with extensive intraneuronal Aβ in transfected cells and transgenic mice expressing this deletion.
A phenotype of combined dementia and cerebral microvasculopathy suggested concurrent increases in brain parenchymal and cerebrovascular beta-amyloid peptide (Aβ) deposition in this patient.
A public-private partnership to establish biomarkers of dementia in Down's syndrome could aid the development of preventive therapies for the dementia associated with both Down's syndrome and Alzheimer's disease, based on the apparent common pathogenic role of amyloid precursor protein in the two conditions.
A significant component of memory loss in APP transgenic mice is apparently caused by soluble A Beta assemblies, but whether and how much of the dementia within individuals afflicted with AD is caused by these A Beta species is unclear.
Also problematic is the alternative hypothesis that, instead of amyloid plaques, it is oligomers of amyloid precursor protein that cause AD.Evidence is presented suggesting amyloid/oligomers as necessary but insufficient causes of the dementia and that, for dementia to develop, requires the addition of cofactors known to be associated with AD.
Although the precise mechanism remains to be elucidated, our data suggest a possible role for APP in modifying the PD phenotype as well as a general contribution of genetic factors to the development of dementia in individuals with PD.
Alzheimer's disease (AD) is the most common cause of dementia that arises on a neuropathological background of amyloid plaques containing beta-amyloid (A beta) derived from amyloid precursor protein (APP) and tau-rich neurofibrillary tangles.
Alzheimer's disease (AD) is the most common cause of dementia and is likely caused by defective amyloid precursor protein (APP) trafficking and processing in neurons leading to amyloid plaques containing the amyloid-β (Aβ) APP peptide byproducts.
AMY plaques are consistently present in familial AD due to presenilin-1 (PS-1), PS-2, and amyloid precursor protein mutations, and they can begin to accumulate before the emergence of dementia.
An elderly man with phenotypic DS and partial trisomy of chromosome 21 (PT21) lacked triplication of APP affording an opportunity to study the role of this gene in the pathogenesis of dementia.
BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48).
Cystatin isolated from chicken egg white, called ovocystatin, has been widely used in the medical and pharmaceutical research due to its structural and biological similarities to human cystatin C. The aim of this study was to assess the effect of administering ovocystatin on the development of dementia-specific cognitive deficits in APP/PS1 transgenic mice.