Neurodegenerative disorders are characterized clinically by insidious onset and slowly progressive course, and are frequently hereditary. Pathologically, these diseases share a common feature: the selective loss of a particular subset of neurons for unknown reasons [e.g. cerebral cortical neurons in ALZHEIMER’S DISEASE (AD) (see Glossary), substantia nigra neurons in PARKINSON’S DISEASE (PD), s...

Neurofibrillary tangles (NFT) are a hallmark of Alzheimer's disease (AD), and their presence correlates with the presence of dementia. A major constituent of NFT is the insoluble paired helical filament which shares some antigenic relationships with normal cytoskeletal elements, particularly neurofilaments. If neurofilament proteins (200, 145-160, and 68 kilodaltons [kd]) participate in the for...

BACKGROUND The relationship between neuropathological lesions and mild, "preclinical," cognitive impairments of Alzheimer disease is poorly understood. Identification of the lesions that are most closely associated with the earliest symptoms of Alzheimer disease is crucial to the understanding of the disease process and the development of treatment strategies to affect its progression. DESIGN...

Background Alzheimer’s disease (AD), Parkinson’s (PD), Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases are responsible for considerable morbidity mortality. With incidence rising with aging, these also represent a growing societal challenge. Pathophysiology involves accumulation of tau (neurofibrillary tangles) Amyloid-β-rich (amyloid plaques) aggregates in AD, α-synucl...

Background Clinical studies indicate that traumatic brain injury (TBI) is linked to an increased risk of dementia during life. However, involving neuropathologically-confirmed cases have shown conflicting results. This study was aimed at assessing a large bank cohort identify any association between TBI and the presence pathologies underlying most commonly found dementias, Alzheimer’s disease (...

An orally bioavailable and blood-brain barrier penetrating analog of the kinase inhibitor K252a was able to prevent the typical motor deficits in the tau (P301L) transgenic mouse model (JNPL3) and markedly reduce soluble aggregated hyperphosphorylated tau. However, neurofibrillary tangle counts were not reduced in the successfully treated cohort, suggesting that the main cytotoxic effects of ta...

Aggregation of amyloid beta peptide into senile plaques and hyperphosphorylated tau protein into neurofibrillary tangles in the brain are the pathological hallmarks of Alzheimer's disease. Despite over a century of research into these lesions, the exact relationship between pathology and neurotoxicity has yet to be fully elucidated. In order to study the formation of plaques and tangles and the...