Amyloid beta-Protein Precursor

In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS.

Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease (AD), including the presence of tau-positive neurofibrillary tangles (NFTs) and ?-amyloid (A?)-related peptides in vulnerable brain regions. Since enhanced cholesterol level, which acts as a risk factor for AD, can increase A?

Sirt1, a mammalian member of the sirtuin gene family, holds great potential for promoting longevity, preventing against disease and increasing cell survival. For example, studies suggest that the beneficial impact of caloric restriction in promoting longevity and cellular function may be mediated, in part, by Sirt1 through mechanisms involving PGC-1alpha, which plays important role in the regulation of cellular metabolism and inflammatory and antioxidant responses. Sirt1 may also interfere with mechanisms implicated in pathological disorders.

The relationship between Alzheimer's disease (AD) and progressive degeneration of the forebrain cholinergic system is very well established, whereas mechanisms linking this disease with cholesterol, apolipoprotein E (apoE) phenotype, and amyloid precursor protein (APP) metabolism have not been fully elucidated even though there is a plethora of publications separately on each of these issues. The intention of this hypothesis is to unify knowledge coming from all of these areas.

Epidemiological evidence implies a role for chronic stress and stress-related disorders in the etiopathogenesis of sporadic Alzheimer's disease (AD). Although chronic stress exposure during various stages of life has been shown to exacerbate AD-related cognitive deficits and neuropathology in AD mouse models, the role of stress exposure during the prenatal period on AD development and progression remained to be investigated.

The aim of this perspective article is to stimulate radical shifts in thinking and foster further discussion on the effective discovery, development, validation, and qualification process of biological markers derived from all available technical modalities that meet the complex conceptual and pathophysiological challenges across all stages of the complex, nonlinear, dynamic, and chronically progressive sporadic Alzheimer's disease (AD).

Alzheimer's disease (AD) is a debilitating illness with no known cure. Nowadays accumulating evidence suggested that the vascular endothelium and chronic hypoperfusion may play important role in pathobiology of AD. The vascular endothelium which regulates the passage of macromolecules and circulating cells from blood to tissue, is a major target of oxidative stress, playing a critical role in the pathophysiology of vascular diseases.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder. A majority of cases manifest as a late onset sporadic form but genetically the disease is divided into familial cases and sporadic cases. The familial form is due to mutations in three major genes (amyloid precursor protein (APP) gene, presenilin1 (PSEN1) gene and presenilin 2 (PSEN2) gene). In contrast, many genetic and environmental factors may contribute to determining the sporadic AD form.

BACKGROUND: Alzheimer's disease (AD) is intimately tied to amyloid-? (A?) peptide. Extraneuronal brain plaques consisting primarily of A? aggregates are a hallmark of AD. Intraneuronal A? subunits are strongly implicated in disease progression. Protein sequence mutations of the A? precursor protein (APP) account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP) may play a more important role in AD etiology.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-? (A?) plaque formation, tau pathology, neurodegeneration and inflammatory processes. Monocytes are involved in inflammation in AD and are recruited to the diseased brain. Recently it has been shown that aberrant epigenetic processes including acetylation are associated with the development of AD.