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.

Cognitive deficits are major disabling impairments associated with autism and schizophrenia. Because theunderlying genetic and cellular mechanisms of such deficits are still poorly understood, mechanism-basedtherapeutic options do not exist, limiting the effective integration of patients into society. Previous clinical workhas shown that executive functions such as working memory and cognitive flexibility start to lag behind fromadolescence to adulthood in individuals with autism and schizophrenia.

Transposable elements, known colloquially as ?jumping genes,? constitute approximately 45% of the humangenome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencingheterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance oftransposable element transcripts. Transposable element activation has recently been identified as a keymediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologicallydefined by deposits of tau protein in the brain.

Medications to help treat addiction exist for many major drugs of abuse, but not for psychostimulants, such asamphetamine, and its congeners. They are also lacking for increasingly used synthetic drugs designed to mimicthe actions of known psychostimulants. Both known and new psychoactive substances continue to pose a majorand increasing public health threat. To develop effective treatments, the mechanisms by which these stimulantsproduce their abuse-related effects need to be fully understood.