The progressive deposition of the beta-amyloid peptide in the brain and its microvasculature is an invariant feature of Alzheimer's disease that appears to precede the onset of dementia by many years.
Since the report of a double mutation at codons 670 and 671 of the amyloid precursor protein (APP) gene identified in two Swedish families with clinically diagnosed Alzheimer's disease (AD), a carrier with dementia has died.
Hereditary cerebral hemorrhage with amyloidosis, Dutch type, caused by a mutation at codon 693 of the amyloid beta precursor protein gene, is characterized by amyloid beta deposition resulting in recurrent strokes and dementia.
However, one patient with a mutation in the APP gene did harbour a novel mtDNA mutation (G to C at position 5705 in the tRNAAsn gene) that might have contributed to the very early onset of dementia in this individual.
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.
We will focus on the regulation of beta-APP cleavage through diverse signal transduction mechanisms and discuss possible points of therapeutic intercession in what has been postulated to be a seminal molecular step in the cascade of events terminating in the onset of dementia, loss of neurons, and eventual death from Alzheimer's disease.
We suggest instead that APP normally functions in the brain as a cell surface signaling molecule, and that a disruption of this normal function of APP is at least one cause of the neurodegeneration and consequent dementia in AD.
We report a mutation at a novel site in APP in a three-generation Iowa family with autosomal dominant dementia beginning in the sixth or seventh decade of life.
Ischemic lesions are characteristic of several hereditary CAA syndromes, including a recently described mutation of the amyloid precursor protein associated with dementia (but not hemorrhagic stroke) in an Iowa family.
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.
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.
Factors which influence Abeta levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.
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.
Patients who progressed to DAT at the 2-year follow-up (n = 12) showed a significant decrease of baseline platelet APP forms ratio values (mean +/- SD, 0.36 +/- 0.28) compared with stable MCI subjects (mean +/- SD, 0.73 +/- 0.32) (P<.01) and patients who developed other types of dementia (mean +/- SD, 0.83 +/- 0.27) (P =.03).
Here frame-shift ubiquitin-B and amyloid precursor protein were immunochemically shown to exist in the brain of high pathology control (HPC) patients with AD pathology but without prior dementia.
The most common familial early onset dementia mutations are found in the genes involved in Alzheimer's disease; the amyloid precursor protein (APP) and the presenilin 1 and 2 (PSEN1 and 2) genes; the prion protein gene (PRNP) may be involved.
Since phosphorylation/dephosphorylation mechanisms are crucial in the regulation of Tau and beta-APP, a superfamily of mitogen-activated protein kinases (MAPKs) has recently emerged as key regulators of the formation of plagues, eventually leading to dementia and AD.
The E693Q mutation in the amyloid beta precursor protein (APP) leads to cerebral amyloid angiopathy (CAA), with recurrent cerebral hemorrhagic strokes and dementia.
This observation has several implications: APP processing abnormalities, believed to be a very early change in Alzheimer disease in neuronal compartment, does occur in extraneuronal tissues, such as platelets, thus suggesting that Alzheimer disease is a systemic disorder; further, our data strongly indicate that a differential level of platelet APP forms can be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia with good sensitivity and specificity.