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Many studies have demonstrated the importance of amyloid precurser protein (APP) in the pathogenesis of Alzheimer’s disease. Nonetheless, the exact mechanism by which APP contributes to the pathogenesis of Alzheimer’s disease is still not clear. Because APP is a glycoprotein, and beca ...

Human genetic studies suggest decreasing amyloid peptide (Aβ) levels in the brain could alter the course of Alzheimer’s disease (AD) (1 -4). Proteolytic cleavages govern the level of Aβ generated from the amyloid precursor protein (APP). β- and γ-cleavages at the amino and carboxyl termini of Aβ p ...

The amyloid precursor protein (APP) is cleaved by at least three proteinases termed the α-, β-, and γ-secretases. Cleavage of APP at the N-terminus of the β-amyloid (Aβ) peptide by β-secretase and at the C-terminus by one or more γ-secretases constitutes the amyloidogenic pathway. In the nonamyloid ...

A detailed understanding of the biochemical events leading to the proteolytic excision of the β-amyloid peptide (A β) from the amyloid precursor protein (APP) has eluded many researchers. This is largely because the measurement of the various APP processing products is technically chal ...

When the amyloid precursor protein (APP) was cloned, Aβ was found to be part of the large APP molecule and it became obvious that at least two endoproteolytic cleavage events are required to release Aβ from its large precursor (1). More than 10 yr later nobody has published definitive identification of ...

A large body of evidence suggests a causative role of β-amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (reviewed in refs. 1 and 2). Aβ is neurotoxic and toxicity requires the formation of amyloid fibrils similar to those found in senile plaques (3). Autosomal dominant mutations linked to Al ...

It has been well established that β-amyloid peptide is the principal protein component of extracellular cerebral amyloid deposits in patients with Alzheimer’s disease (1,2). β-Amyloid is derived from a large precursor protein, amyloid precursor protein (APP), which is an integral mem ...

Amyloid precursor protein (APP) and Alzheimer’s disease are irrevocably linked, as APP is cleaved to form the Aβ peptides that are the major components of amyloid plaques. One of the most resilient hypotheses about the cause of AD centers on the Aβ peptide; all genetic causes and risk factors can be fit ...

Mutations in two related genes, PS1 (1) and PS2 (2,3) located on chromosomes 14 and 1, respectively, account for the majority of early onset cases of familial Alzheimer’s disease (FAD). PS1 and PS2 are predominantly localized in the endoplasmic reticulum and Golgi (4-7). PS1 is a 467 amino acid peptide pr ...

In 1907, Alois Alzheimer published an account (1) of a 51-year-old female patient, Auguste D., who suffered from strong feelings of jealousy towards her husband, increased memory impairment, disorientation, hallucinations, and often loud and aggressive behavior. After four and a half yea ...

The majority of familial Alzheimer’s disease (AD) cases are linked to mutations of the presenilin 1 and 2 (PS1, PS2) genes on chromosomes 14 and 1, respectively (1-3). PS1 and PS2 are about 67% identical in amino acid sequence. Based on hydrophobicity analysis, the presenilins are predicted to have mul ...

Familial Alzheimer’s disease (FAD) is a genetically heterogeneous disorder that is caused by defects in at least three early onset genes (age of onset:

The phosphorylation of presenilin (PS) proteins was initially analyzed in cultured cells overexpressing the respective proteins. These studies revealed that the homologous PS proteins are differentially phosphorylated in vivo. Fulllength PS2 was found to be constitutively ...

The genes encoding presenilin-1 (PS1) and presenilin-2 (PS2) were identified as the genes that harbour mutations that cause more than 60% of early onset familial Alzheimer’s disease cases (FAD) (1-3). So far, more than 40 missense mutations have been described for presenilin-1 and two have been fo ...

The role of Aβ accumulation in the pathogenesis of Alzheimer’s disease (AD) is supported by genetic studies showing that mutations in the amyloid-β precursor protein (APP) that alter Aβ production are linked to a subset of familial AD (FAD) cases with autosomal penetrance (reviewed in ref. 1). Sev ...

The β-amyloid precursor protein (APP) is connected to Alzheimer’s disease by both biochemistry and genetics. As the source of the major constituent of amyloid plaques, APP has been the subject of many studies of its expression and metabolism. The accumulation of amyloid β-peptide (Aβ) in these p ...

There has been gratifying progress in the development of drugs for Alzheimer’s disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an “effective” therapy has matured considerably ov ...

Since the first description of Alzheimer’s disease (AD) at the beginning of the century until relatively recently, it was customary to define Alzheimer’s disease as occurring in the presenium. The same neuropathological changes occurring in brains over the age of 65 were called “senile dem ...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in which abnormal filamentous inclusions accumulate in dystrophic and dying nerve cells. These inclusions have been described as neurofibrillary tangles (NFTs) of which paired helical filaments (PHFs) are t ...

Tau was originally isolated from brain microtubules and shown to be a microtubule-associated protein (MAP) that promoted tubulin polymerization (1). It is largely confined to axons, where it is the major MAP. It promotes microtubule nucleation, elongation, and bundling, and stabilizes ...