Alzheimer's disease

The pathology of Alzheimer's disease (AD) remains elusive. Competing evidence links amylois \U+fffd\-peptide (A\U+fffd\) amyloid formation to the phenotype of AD (1). The mechanism of amyloid fibril formation has been an ongoing investigation for many years. A\U+fffd\10-23 peptide, a fragment of A\U+fffd\1-42 peptide, contained crucial hydrophobic core residues (2). In this study, an investigation was launched to study the aggreagation process of A\U+fffd\1023 peptide and its ability to form amyloid fibrils. Furthermore, the presence of its hydrophobic core showed importance for its ability to aggregate and form amyloid fibrils. Thereafter, the inhibition of A\U+fffd\1-42 peptide aggregation was studied by using pyrimidine-based compounds. A\U+fffd\1-42 peptides, known to be neurotoxic, aggregate to form amyloid fibrils (3). This investigation may provide insight into the development of novel small molecular candidates to treat AD.

Data was provided by researchers of the Einstein Aging Study (EAS) of the Albert Einstein College of Medicine, Yeshiva University whom statistically analyzed data from the Bronx Aging Study cohort, concluding that participation in cognitive leisure activities and one physical activity, dancing, were associated with a reduced risk of dementia [1]. We explore data from a second (the EAS) cohort, utilizing Cox Proportional-Hazards and extended Cox regression [13]. Cognitive leisure activities in general, and particularly doing crossword puzzles, reading books, watching television, and emailing are associated with a reduced risk of dementia. Doing aerobics, learning computer programming, babysitting, dancing, jogging singing, and weight training are associated with an increased risk of dementia. Participation in cognitive leisure activities in general, and reading books in particular, remains highly significant even after adjustment for well-known risk factors [14] such as: age, cognitive status, depression, medical illnesses, gender, ethnicity, education and economic status.

This study aimed to understand the differences in strength or coordination of brain regions involved in processing faces in the presence of aging and/or progressing neuropathology (Alzheimer's disease). To this end, Experiment 1 evaluated age-related differences in basic face processing and the effects of familiarity in face processing. Overall, face processing in younger (22-35yrs) and older participants (63-83yrs) recruited a broadly distributed network of brain activity, but the distribution of activity varied depending on the age of the individual. The younger population utilized regions of the occipitotemporal, medial frontal and posterior parietal cortices while the older population recruited a concentrated occipitotemporal network. The younger participants were also sensitive to the type of face presented, as Novel faces were associated with greater mean BOLD activity than either the Famous or Relatives faces. Interestingly, Relatives faces were associated with greater mean B OLD activity in more regions of the brain than found in any other analysis in Exp. 1, spanning the inferior frontal, medial temporal and inferior parietal cortices. In contrast, the older adults were not sensitive to the type of face presented, which could reflect a difference in cognitive strategies used by the older population when presented with this type of face stimuli. Experiment 2 evaluated face processing, familiarity in face processing and also emphasized the interactive roles autobiographical processing and memory recency play in processing familiar faces in mature adults (MA; 45-55yrs), older adults (OA; 70-92yrs) and patients suffering from Alzheimer's disease (AD; 70-92yrs).

Alzheimer's disease (AD) is an increasingly common neurological disorder that mainly affects memory formation and retention. It is characterized by unique intercellular neurofibrillary tangles and extracellular beta-amyloid plaques. Histone deacetylase inhibitors (HDACi's) are competitive antagonists against histone deacetylases, causing histone acetyltransferases to acetylate the genome unregulated. This thesis investigates the use of new histone deacetylase inhibitors on recovering memory in a mouse model of Alzheimer's disease. By use of a fear conditioning paradigm, we have shown that these HDACI's increase memory in AD mice, but show either no effect or a positive effect in wild-type mice. Future experiments will investigate the efficacy of compound 966 and the spine density of hippocampal brain slices after fear conditioning trials.