Staining of Amyloid Beta (Abeta) Using (Immuno) Histochemical Techniques and Abeta42 Specific Peptides

In the elderly, Alzheimer’s disease (AD) is the most common form of dementia (Hebert et al., 2003). The two pathologies that characterize the disease are the presence of large numbers of intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques in the brain (e.g., Braak and Braak, 1991; 1998; Selkoe, 2001). Neurofibrillary tangles consist of hyperphosphorylated, twisted filaments of the cytoskeletal protein tau (e.g., Duff, 2006), whereas plaques are primarily made up of amyloid ┚(A┚ [Selkoe, 2001; Dickson and Vickers, 2002]), a 39-43 amino acid long peptide derived from the proteolytic processing of the amyloid precursor protein (APP [Selkoe, 2001; Vetrivel and Thinakaran, 2006]). When APP is sequentially cleaved by the ┚-secretase and ┛-secretase, one of the resulting breakdown product is A┚, in contrast, initial cleavage by ┙-secretase (in the middle of the A┚ sequence) leads to production of APPs┙ and the C83 peptide (Selkoe, 2001). Most cases of AD are sporadic, however approximately 5 % of AD cases are familial (Price and Sisodia, 1995; Selkoe, 2001), these cases are related to mutations in the genes for APP, and presenilin 1 and 2 (PS1 and PS2 [Price and Sisodia, 1995; Hardy, 1997; Selkoe, 2001]). Transgenic mice expressing mutated human AD genes offer a powerful model to study the role of A┚ in the development of pathology (e.g., Duff and Suleman, 2004; McGowan et al, 2006). The present study employs three lines of transgenic mice expressing both human APPswe and/or PS1 mutations. These lines of mice develop elevated levels of A┚42 at different ages, and at different locations (Van Groen et al., 2005; Wang et al., 2003).