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.
Here, we describe a novel missense mutation in the amyloid precursor protein (APP) causing a lysine-to-asparagine substitution at position 687 (APP770; herein, referred to as K16N according to amyloid-β (Aβ) numbering) resulting in an early onset dementia with an autosomal dominant inheritance pattern.
Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein and tau alterations in this type of dementia remains controversial.
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.
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.
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.
In order to assess the frequency of mutations in the known Alzheimer's disease causative genes in Turkish dementia patients we screened amyloid precursor protein (APP), PSEN1 and PSEN2 for mutations in a cohort of 98 Turkish dementia families.
Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias.
Genetic studies show that a simple duplication of the Aβ precursor (APP) gene, as occurs in Down syndrome (trisomy 21), with a 1.5-fold increase in expression, can cause dementia with the complete AD associated neuropathology.
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.
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.
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.
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.
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).
We explored how levels of endocytic proteins, APP, its metabolites, secretase enzymes, and tau varied with age in cortical brain samples from men of three age ranges (young [20-30], middle aged [45-55], and old [70-90]) with no symptoms of dementia.
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.
Effect of early intervention with extract of Huannao Yicong Decoction (还脑益聪方) on the pathologic picture of hippocampus and neurocyte apoptosis in APP transgenic mice model of dementia.
Neuropsychiatric symptoms have been reported as prodromal symptoms of AD-like dementia and soluble forms of beta amyloid peptide (Aβ), the main constituent of insoluble plaques typical of AD brains, have been implicated in such an effect.
Scrutiny of the evidence generated so far reveals and a lack of understanding of the wider APP proteolytic system and how narrow research into the dementia syndrome has been to date.
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.
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.