Basic Science and Pathogenesis.

Background: Sleep dysfunction is commonly seen in Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP), potentially worsening these conditions. Investigating early neuropathological changes in human sleep-promoting neurons, which often precede cognitive decline, is crucial for understanding the basis for sleep dysfunction as possible treatments yet remain underexplored. We used postmortem brains of AD and PSP patients to quantify neuronal numbers and tau burden in the intermediate nucleus of the hypothalamus (IntN), VLPO analog, known for its role in sleep maintenance.

Basic Science and Pathogenesis.

Background: Excessive daytime sleepiness is a common and early symptom of Alzheimer's disease (AD). The subcortical wake-promoting neurons in the lateral hypothalamic area, tuberomammillary nucleus (TMN), and locus coeruleus synchronize to maintain wakefulness/arousal. Although significant neuronal decline occurs in wake-promoting regions, the TMN histaminergic neurons remain relatively more intact than orexinergic and nor-adrenergic neurons.

Basic Science and Pathogenesis.

Background: The proteasome plays key roles in synaptic plasticity and memory by regulating protein turnover, quality control, and elimination of oxidized/misfolded proteins. Here, we investigate proteasome function and localization at synapses in Alzheimer's disease (AD) post-mortem brain tissue and in experimental models.

Method: We used primary hippocampal cultures, amyloid-β oligomers (AβO)-injected or transgenic animal models, and human brain tissue to determine brain proteasome function and subcellular localization.

Basic Science and Pathogenesis.

Background: The atherosclerotic plaque in carotid arteries has been associated with dementia. Clinic radiological studies in older adults suggest that the composition of atherosclerotic plaque in the carotid artery can predict vascular dementia (VD) or mixed dementia. The proposed study aims to assess components of atherosclerotic plaques in the carotid arteries, particularly concerning cerebrovascular lesions using racially diverse autopsy samples.

Basic Science and Pathogenesis.

Background: Lewy body disease (LBD) is a neurodegenerative condition marked by the accumulation of neuronal alpha-synuclein, leading to both Parkinson's disease and Lewy body dementia. It is regarded as the second most common neurodegenerative disease associated with aging. However, there is limited knowledge of LBD prevalence in the general population, particularly among non-whites.