Antibodies for Alzheimer's & Neurodegenerative Diseases' Research

Alzheimer's Disease (AD) and Parkinson's Disease (PD) are among the leading neurodegenerative diseases of the central nervous system (CNS).

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 β-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.

PD is a slowly progressing motor system neurodegeneration characterized by akinesia, rigidity and resting tremor. Neuropathologically PD is characterized by loss of dopaminergic cell bodies in the substantia nigra, resulting in a reduced supply of dopamine to the basal ganglia. The high metabolic rate of the substantia nigra combined with high content of oxidizable species and iron, high levels of reactive oxygen species (ROS) and low level of antioxidants, all serve to initiate/propagate apoptosis of the dpaminergic neurons. An additional trigger for PD is the α-synuclein protein. Lewy bodies are composed of cytoskeletal proteins including α-synuclein, ubiquitin, synaptophysin and tau, with α-synuclein as the major component. α-Synuclein can form protein aggregates which are believed to lead to the pathogenesis of Lewy body formation.

	Figure 1. Immunohistology of rat cholinergic neurons using Anti-Vesicular Acetylcholine Transporter (VaChT)
	Figure 2. Immunoblotting using Anti-Nicastrin
	Figure 3. Immunoblotting using Anti-BACE-1 (LK-16)
	Figure 4. Immunohistochemistry of Alzheimer's Disease brain section using Anti-b-Amyloid Protein (1-40)

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