Berislav V Zlokovic Blas Frangione and Jorge Ghiso

Brain Power Genesis

Natural Treatment for Dementia Discovered

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Deposition of amyloid p peptide (Ap) in the central nervous system (CNS) and cerebral vessels occurs during normal aging and is accelerated by Alzheimer's disease (AD).1,2 AD is the most common form of human amyloidosis and the major cause of dementia, affecting >5% of the population over the age of 65 years. Neuropathologically, AD is characterized by:

1. Intraneuronal deposits of neurofibrillary tangles (NFT);

2. Parenchymal amyloid deposits—neuritic plaques;

3. Vascular amyloidosis; and

4. Synaptic loss.

Ap is considered to be implicated in neuropathogenesis and the development of cere-brovascular pathology in AD and related disorders.1-8 Recent studies from our and other laboratories suggest a major role for the blood-brain barrier (BBB) and cerebrospinal fluid (CSF) clearance in regulating the concentrations of Ap in brain and cerebral vasculature.9-20 The process of Ap amyloid formation is highly tissue-specific, and normally with aging occurs in brain extracellular fluid (ECF) space, in the walls of cortical and leptomeningeal vessels and in the choroid plexus (CP) in humans, nonhuman primates and some mammalian species.1,21 Specific predisposing genetic factors (e.g., apolipoprotein E4 (apoE4) genotype, mutations in amyloid-p-precursor protein (pPP), presenilin 1 and 2 genes, a2-macro-globulin), age-dependent mechanisms (e.g., expression of specific receptors, binding proteins) and/or provocative stimuli (e.g., cytokines) may increase the aggregation and/or enhance the cytotoxicity of Ap, and are important for the development of AD and Ap-related pathology.1 Apolipoproteins J and E (apoJ, apoE) may critically influence fibrillogenesis, cytotoxicity, transport across biological membranes and cell-specific uptake of Ap within the CNS.

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