Antibodies for Alzheimer′s Disease

Alzheimer¢s Disease (AD) is the most common form of dementia seen in our aging society, and the focus of most of the research on neurodegenerative diseases. Since its discovery more than 100 years ago, AD has been known to cause the loss of cognitive function. The neurological hallmarks are the presence of neuritic plaques and neurofibrillary tangles of proteins in brain tissue. The inevitable result is death, at which time a definitive diagnosis is possible.

AD is characterized by gradual loss of cognitive functions. Hallmark pathohistological findings of AD include widespread neuronal degeneration, neuritic plaques containing β-amyloid (Aβ) and tau-rich neurofibrillary tangles (NFT). A cholinergic deficit is one of the primary features of Alzheimer′s disease (AD), resulting from loss of cholinergic neurons in the basal forebrain, hippocampus and cerebral cortex. The synthesis, storage and release of acetylocholine (ACh) requires the expression of several specialized proteins, including choline acetyltransferase (ChAT) and the vesicular ACh transporter (VAChT).

Mutations in three genes, the amyloid precursor protein (APP) on chromosome 21, presenilin-1 (PS-1) on chromosome 14 and presenilin-2 (PS-2) on chromosome 1, are all involved in autosomal dominant inherited AD or early onset familial AD (FAD). Other genes that are considered susceptibility or risk factors for AD include the apoliporotein E (ApoE ε4 variant), α2-macroglubulin and several mitochondrial genes. Abnormal processing of the -amyloid precursor protein (APP) and extracellular accumulation of β-amyloid peptides into neuritic plaques has been proposed to cause AD. APP is cleaved sequentially by the proteolytic enzymes BACE (identified as β-secretase) and γ-secretase to produce β-amyloid peptides with Aβ40 and Aβ42 being the predominant forms. Nicastrin (Nct), a type I transmembrane glycoprotein and a component of the PS complex, is essential for γ-secretase activity. Mutations in the APP, PS1, and PS2 genes all produce an increase of in Aβ42. NFT found in AD are made up of aggregated and hyperphosphorylated tau protein. Additional abnormal tau modifications found in AD also include glycation, oxidation, ubiquitination and truncation, ultimately leading to disruption of neurofilament-microtubule interaction and disruption of neuronal transport.

The early detection and risk assessment of AD is of great interest to researchers, but much of the research focuses on the development of effective treatment strategies.Sigma-Aldrich offers antibodies for use in Alzheimer¢s Disease research. These isolated antibodies are produced in a range of host species, with reactivity in humans and a variety of animals.