Alzheimer s disease senile plaques

Lovell M A, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. 1998. Copper, iron and zinc in Alzheimer s disease senile plaques. J Neurol Sci 158 47-52. 

Ginsberg SD, Crino PB, Hemby SE, Weingarten JA, Lee VM, Eberwine JH, et al. Predominance of neuronal mRNAs in individual Alzheimer s disease senile plaques. Ann Neurol 1999 45(2) 174-181. 

Lovell MA, Robertson ID, Teesdale WJ, Campbell JL, Markesbery WR (1998) Copper, iron and zinc in Alzheimer s disease senile plaques. J Neurol Sci 158 47-52 Lu Z, Nie G, Li Y, Soe-Lin S, Tao Y, Cao Y, Zhang Z, Liu N, Ponka P, Zhao B (2009) Overexpression of Mitochondrial Ferritin Sensitizes Cells to Oxidative Stress Via an Iron-Mediated Mechanism. Antioxid Redox Signal 11(8) 1791-1803 Luchsinger JA, Tang MX, Shea S, Mayeux R (2003) Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 60 203-208... 

Edelstein-Keshet, L., Spiros, A. Exploring the formation of Alzheimer s disease senile plaques in silica. J. Theor. Biol. 216(3), 301-326 (2002). http //dx.doi.org/l0.l006/ jtbi.2002.2540... 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

Evidence for a neuroimmunological involvement in Alzheimer s disease is accumulating. Activation of the complement cascade by beta amyloid (Rogers et al., 1992), the recruitment, proliferation and activation of microglia in intimate juxtaposition to the senile plaques (Davis et al., 1992), and the increased synthesis of microglia-derived pro-inflammatory cytokine interleukin-1 (Griffin et al., 1989) is indicative of a chronic inflam-... 

Neuritic (senile) plaques Microscopic lesions composed of fragmented axon terminals and dendrites surrounding a core of amyloid seen in the cerebral cortex in Alzheimer s disease. 

Alzheimer s disease Neocortex, hippocampus (J Peptide 4R, 3R tau Diffuse and senile plaques,... 

Amyloid protein A 42-amino acid protein found in the core of the microscopic senile plaques in the brains of individuals with Alzheimer s disease, p-amyloid protein is synthesised from the much larger amyloid precursor protein (APP). 

Numerous in vitro studies have implicated ROS in neuronal death [Leonardi and Mytilineou, 1998], and different markers of oxidative stress are found in postmortem examination of brain tissues from patients with neurodegenerative disorders [Sayre et al., 2001], DNA oxidation, protein oxidation, and lipid peroxidation have been reported in brain regions containing neurofibrillary tangles and senile plaques from Alzheimer s disease (AD) patients [Lovell and Markesbery, 2007 Polidori et al., 2007], Dopaminergic neurons in the substantia nigra of brains of Parkinson s disease (PD) patients also exhibit hallmarks of oxidative stress [Giasson et al., 2002]. 

Generally, but not invariably, postmortem macroscopic examination of the brain reveals cerebral atrophy with narrowed convolutions, widened sulci, and enlarged lateral and third ventricles. On microscopic examination brain specimens from patients with a clinical diagnosis of Alzheimer s disease are characterized by widely spread cortical senile plaques, neurofibrillary tangles, and granulovascular degeneration. 

Alzheimer s disease (AD) along with vascular and mixed dementia is the commonest form of dementia affecting older people and accounts for 60-65% of dementia cases, whereas vascular dementia and mixed dementia account for 15-20% of the cases each (1). The Brain of individuals with AD manifest two characteristic lesions senile plaques and intracellular neurofibrillary tangles of the hyperphosphorylated tau protein (2). The amyloid fi-protein (Afi) is the principal component of the senile plaques. It is a peptide of 39-43 amino acids, derived from a larger precursor, the amyloid precursor protein (APP) (Fig. 1). 

---