Potential Therapy For Alzheimer's Disease Research Articles

A chronic physiological rat model of dementia

We have developed an aging rat model that mimics specific pathology reported in dementia, particularly Alzheimer's disease (AD). The model involves subjecting rats to chronic cerebrovascular insufficiency (CVI) for 1–9 weeks. Gross and sensory-motor function remains normal but spatial memory acquisition and retention are impaired after 1 week and worsens progressively with time. In vivo [ 31P]NMR spectroscopy evaluation in CVI animals showed membrane phospholipid synthesis increase in the hippocampal-cortex region of affected animals which increases with time. Post-mortem examination revealed that CA1 neurons can express selective damage 1 week after CVI and the number of CA1 neurons thus affected increases in proportion with time. Moreover, there is progressive increase in GFAP hypertrophy and hyperplasia in the hippocampal region during the 9-week observation period. Reduction of microtubulc-associated protein 2 and pre-terminal noradrenergic varicosities in the hippocampus-cortex is seen after 9 weeks but not 1 week of CVI. All the above changes have been reported in AD-affected brains. The present CVI model appears as a useful screen in investigating potential therapy for AD as well as increasing understanding of this disorder.

Studies of Amyloid β‐Protein Precursor Expression in Alzheimer's Disease

The generation of the beta/A4 peptide and its accumulation into insoluble amyloid deposits represent key events in the neuropathologic process of Alzheimer's disease (AD). This posit has gained further support from recent reports that beta/A4 is directly responsible for the death of neurons. Potential therapies for AD aimed at abating the production of beta/A4 will require the basic knowledge of where it comes from. The 4.2-kD peptide is derived from a much larger amyloid precursor protein (APP) encoded by a gene that produces multiple transcripts. Employing in situ hybridization with biotinylated oligonucleotide probes, we set out to define which forms of the precursor are synthesized in affected regions of AD brain (e.g., hippocampal formation) and to determine the cell populations responsible for their manufacture.