Neurofibrillary Tangles

Publication Title: 
European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology

Alzheimer's disease (AD) appears to be a uniquely human condition, which is possibly attributable to our expanded longevity and peculiar capacity for episodic memory. Due to a lack of naturally-occurring animal model for investigating AD pathogenesis, our knowledge about the disease must be derived from correlational observation of humans, or from animal models produced by genetic manipulation of known risk factors in humans.

Author(s): 
Reid, Andrew T.
Evans, Alan C.
Publication Title: 
Aging Cell

Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia. Pathological tau is hyperphosphorylated and aggregates to form neurofibrillary tangles. The molecular mechanisms leading to tau accumulation remain unclear and more needs to be done to elucidate them. Age is a major risk factor for all tauopathies, suggesting that molecular changes contributing to the aging process may facilitate tau accumulation and represent common mechanisms across different tauopathies.

Author(s): 
Caccamo, Antonella
MagrÏ, Andrea
Medina, David X.
Wisely, Elena V.
LÛpez-Aranda, Manuel F.
Silva, Alcino J.
Oddo, Salvatore
Publication Title: 
Journal of Neurology, Neurosurgery, and Psychiatry

The genetic analysis of common neurological disorders will be a difficult and protracted endeavour. Genetics is only one of many disciplines that will be required but it has already thrown considerable light on the aetiology of several major neurological disorders through the analysis of rare inherited subgroups. The identification of individual susceptibility genes with variants of smaller effect will be more difficult but there is no sharp demarcation between large and small genetic effects, so that many new and important insights will emerge using existing and new technologies.

Author(s): 
Wright, A. F.
Publication Title: 
Frontiers in Bioscience (Elite Edition)

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder. A majority of cases manifest as a late onset sporadic form but genetically the disease is divided into familial cases and sporadic cases. The familial form is due to mutations in three major genes (amyloid precursor protein (APP) gene, presenilin1 (PSEN1) gene and presenilin 2 (PSEN2) gene). In contrast, many genetic and environmental factors may contribute to determining the sporadic AD form.

Author(s): 
Piaceri, Irene
Nacmias, Benedetta
Sorbi, Sandro
Publication Title: 
Journal of the American Dental Association (1939)

BACKGROUND: Numerous studies have linked dementia to the subsequent deterioration of oral health. Few investigators, however, have examined oral disease as a potential risk factor in the development of dementia. The authors conducted a study to investigate a potential association between a history of oral disease and the development of dementia. METHODS: Longitudinal dental records supplemented data collected from 10 annual cognitive assessments of 144 Milwaukee participants in the Nun Study, a longitudinal study of aging and Alzheimer disease, who were 75 to 98 years old.

Author(s): 
Stein, Pamela Sparks
Desrosiers, Mark
Donegan, Sara Jean
Yepes, Juan F.
Kryscio, Richard J.
Publication Title: 
Archives of Neurology

BACKGROUND: The sortilin-related receptor SorLA/LR11 (LR11) is a transmembrane neuronal sorting protein that reduces beta-amyloid precursor protein trafficking to secretases, notably BACE1 that generates beta-amyloid, the principal component of senile plaques in Alzheimer disease (AD). LR11 protein is reduced in patients with late-onset AD, and LR11 polymorphisms have been associated with late-onset AD.

Author(s): 
Ma, Qiu-Lan
Galasko, Douglas R.
Ringman, John M.
Vinters, Harry V.
Edland, Steven D.
Pomakian, Justine
Ubeda, Oliver J.
Rosario, Emily R.
Teter, Bruce
Frautschy, Sally A.
Cole, Greg M.
Publication Title: 
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry

OBJECTIVES: Amyloid senile plaques and tau neurofibrillary tangles are neuropathologic hallmarks of Alzheimer disease, which may be associated with mild cognitive impairment (MCI) or mood and anxiety symptoms years before the dementia diagnosis.

Author(s): 
Lavretsky, Helen
Siddarth, Prabha
Kepe, Vladimir
Ercoli, Linda M.
Miller, Karen J.
Burggren, Alison C.
Bookheimer, Susan Y.
Huang, Sung-Cheng
Barrio, Jorge R.
Small, Gary W.
Publication Title: 
Acta Neuropathologica

Tauopathies represent a class of neurodegenerative disorders characterized by abnormal tau phosphorylation and aggregation into neuronal paired helical filaments (PHFs) and neurofibrillary tangles. AMP-activated protein kinase (AMPK) is a metabolic sensor expressed in most mammalian cell types. In the brain, AMPK controls neuronal maintenance and is overactivated during metabolic stress.

Author(s): 
Vingtdeux, Valérie
Davies, Peter
Dickson, Dennis W.
Marambaud, Philippe
Publication Title: 
The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry

OBJECTIVES: To determine whether psychological well-being in people with mild cognitive impairment (MCI), a risk state for Alzheimer disease (AD), is associated with in vivo measures of brain pathology. METHODS: Cross-sectional clinical assessments and positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles, were performed on middle-aged and older adults at a university research institute.

Author(s): 
Chen, Stephen T.
Siddarth, Prabha
Saito, Nathan Y.
Rueda, Flori
Haight, Taylor
Ercoli, Linda M.
Miller, Karen J.
Lavretsky, Helen
Barrio, Jorge R.
Bookheimer, Susan Y.
Small, Gary W.
Merrill, David A.
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