Amyloid core

Frautschy, S.A., Baird, A. and Cole, G.M. (1991). Effects of injected Alzheimer 0-amyloid cores in rat brain. Proc. Natl Acad. Sci. USA 88, 8362-8366. 

A better understanding of the biochemical nature of the amyloid core of the NP was only gained decades after its initial description. In 1984, it was discovered that boiling the plaque cores in formic acid could dissociate them, revealing that they were proteinaceous in nature and composed primarily of the Ap peptide [3]. 

Balguerie, A., Dos Reis, S., Coulary-Salin, B., Chaignepain, S., Sabourin, M., Schmitter, J. M., and Saupe, S.J. (2004). The sequences appended to the amyloid core region of the HET-s prion protein determine higher-order aggregate organization in vivo. J. Cell Sci. 117, 2599-2610. 

Roher AE, Lowenson JD, Clarke S, Wolkow C, Wang R, Cotter RJ, Reardon IM, Ziircher-Neely HA, Heinrikson RL, Ball MJ, Greenberg B. (1993) Structural alterations in the peptide backbone of beta-amyloid core protein may account for its deposition and stability in Alzheimer s disease. J Biol Chem268 3072-3083. 

FIGURE 12—14. Postmortem brain pathology defines what Alzheimer s disease is. Shown here are abnormal degenerative structures called neuritic plaques with amyloid cores. 

The mechanism of AD pathogenesis still remains unclear. However, one mechanism, amyloid (3 (A(3) accumulation, may be due to the disturbance in metal homeostasis in AD brains [Strausak et al., 2001]. A(3 peptides are the major constituents of the amyloid core of senile plaques, which are derived from the amyloid precursor protein (APP) and are secreted into extracelluar spaces. Both APP and A(3 contain a copper-binding domain [Hesse et al., 1994 Atwood et al., 1998]. High concentrations of copper, zinc, and iron have been found within the amyloid deposits in AD brains [Lovell et al., 1998], A(3 peptides can be rapidly precipitated by copper under mildly acidic conditions and by zinc at low physiological (submicromolar) concentrations [Bush et al., 1994], An age-dependent binding between A(3 peptides with excess brain metals (copper, iron, and zinc) induces A(3 peptides to precipitate into metal-enriched plaques [Bush, 2002],... 

Alzheimer disease is a very heterogeneous disorder that is characterized by dementia due to plaque formation, with a central amyloid core, in frontal and temporal lobes. Although small mononuclear infiltrates have been described, they are not held... 

The amyloid cores were strongly immunoreactive with antisera to the mid-region of the molecule, and the periphery of the cores was immunostained by antibodies to N- or C-terminal domains. In addition, the antisera to PrP labeled large areas of tbe neuropil that did not show the tinctorial and optical properties of amyloid, suggesting that amyloid deposition in GSS is accompanied by accumulation of PrP peptides, which are not assembled into amyloid fibrils. 

The senile plaques represent extracellular round or ovoid structures, their diameters ranging between 1.5 and 20 nm. Typically, these plaques consist of three components abnormal nerve processes, glial processes and a central or amyloid core. There are different stages in plaque development primitive plaques consisting of neuritic components only, the classic plaque with central amyloid core surrounded by dystrophic neurites and, in the final stage, the bumed-out plaque with... 

Further processing of plO by y-secretase yields truncated Ap fragments of about 3 kDa (p3) and the APP intracellular domain (AlCD). p3 is generally not found in amyloid cores of classical plaques, or in amyloid deposits in the cerebral vasculature. The AICD fragment can form multiprotein complexes, which are transported to the nucleus and may have a role in nuclear signaling (Shoji et al., 1992). 

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