Aging is the greatest known risk factor for Alzheimer's disease (AD), the most common cause of dementia inolder individuals. However, effective AD therapies remain elusive, which underscores the need to betterunderstand disease etiology and its co-occurrence with advanced age. The apolipoprotein E4 (apoE4) allele isthe strongest genetic risk factor for late-onset AD and it is associated with decreased lifespan. The apoEprotein is crucial to lipid homeostasis through its regulation of cholesterol, triglyceride and phospholipidmetabolism in the blood and the brain.

Alzheimer's disease (AD) is the most common neurodegenerative disease affecting millions of Americans.Neurons have a large amount of polyunsaturated fatty acids in membrane phospholipids that are vulnerable toattack by reactive oxygen species to result in lipid peroxidation. Lipid peroxidation is increased in AD brains andis believed to play a key role in driving neurodegeneration of AD. However, supplementation of lipid solubleantioxidants yields only mixed results in clinical trials. So the importance of lipid peroxidation in AD remainsunproven.

While the etiology of Alzheimer's disease (AD) is multifactorial and complex, results from epidemiological,clinical, and laboratory animal studies implicate traumatic brain injury (TBI) as an important risk factor for ADand dementia. However, the mechanisms by which TBI increases the risk of AD are largely unknown.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly and a majority of AD cases issporadic without known causes. While the etiology of AD is multifactorial and complex, growing evidencesuggests that traumatic brain injury (TBI) is a risk factor for development of AD and dementia. Repetitive TBIcauses chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease. Pathological TDP-43 inclusions are one of the important hallmarks of neuropathology in CTE.

The brain uses previous activity in order to adapt to an ever changing environment. This history

dependence adaptation takes place at all scales of organization of the nervous system. The objective of this theory

project is to develop a shared formalism that can be applied to multiple history dependent phenomena, from the

biochemical reactions that underlie synaptic plasticity, to the emergent patterns in complex neural networks. At

the core of this formalism is the recognition that most models of neuronal activity are based on the classical

Genetic testing has greatly advanced diagnosis of early onset epilepsy. In spite of the expanding number of monogenetic disorders, such as epilepsy in patients with Aristaless-related homeobox gene (ARX) mutations, many of these rare diseases do not have a validated experimental model and thus suffer from limited understanding of the mechanisms of brain development and epileptogenesis. ARX is a transcription factor which is widely expressed in the developing and adult brain, skeletal muscle, pancreas, and testes.

Generalization, the tendency to respond in similar ways in different situations, can be adaptive or maladaptive, depending on the context. For example, generalizing fear of a real threat to other similar dangerous contexts can be important for survival; conversely, displaying fear in safe environments is detrimental. The ventral hippocampus (VH) is in a key position to modulate valence and provide contextual information that allows for selective or generalized responses. Yet little is known about how this area modulates these behaviors.

Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders such as Parkinson’s disease. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities.