The nuclear envelope is a lipid bilayer that encases the genome and provides a physical boundary betweenthe cytoplasm and the nucleoplasm. While the nucleus is typically depicted as a sphere encircled by a smoothsurface of nuclear envelope, the smooth exterior can be interrupted by tubular invaginations of the nuclearenvelope into the deep nuclear interior. Such structures are termed the ?nucleoplasmic reticulum.?

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 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.

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.