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 ___ Neurological Disorders: Alzheimer's Disease ___ |
Alzheimer's Disease - Brain Regions and their Dysfunctions
Alzheimer's Disease"Overall, limbic structures showed significant atrophy in AD patients compared with normal control subjects. Differences (p < 0.05) were found in all limbic regions except the anterior cingulate cortex. The greatest percentage volumetric losses occurred in the septal area (34%), hippocampus (28%), amygdala (21%), parahippocampal cortex (21%), and posterior cingulate cortex (20%). Combining volumetric measures of amygdala and septal area distinguished patients with AD from normal control subjects with 93% accuracy." S"Microglial activation similar to that which occurs in peripheral macrophages during inflammatory attack was first demonstrated in the Alzheimer's disease (AD) brain two decades ago." S "The progression of AD, with slowly increasing damage in brain parenchyma preceding the onset of symptoms, suggests that tissue distress triggering damage signals drives neuroinflammation. These signals via toll-like receptors, receptors for highly glycosylated end products, or other glial receptors activate sensors of the native immune system, inducing the anomalous release of cytokines and promoting the neurodegenerative cascade, a hallmark of brain damage that correlates with cognitive decline." S "Microglia, the resident macrophages in the brain, are strongly implicated in the pathology and progressively degenerative nature of AD. Specifically, microglia are activated in response to both beta amyloid (Abeta) and neuronal damage, and can become a chronic source of neurotoxic cytokines and reactive oxygen species (ROS). NADPH oxidase is a multi-subunit enzyme complex responsible for the production of both extracellular and intracellular ROS by microglia. Importantly, NADPH oxidase expression is upregulated in AD and is an essential component of microglia-mediated Abeta neurotoxicity." S "Through a comparative immunohistochemical analysis we confirm the presence of abundant chitin-like deposition in AD brains (...)" S "Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss." S "In Alzheimer's disease, the basal forebrain cholinergic neurons are selectively vulnerable, putatively because of their expression of the cell death mediator p75(NTR) (the common neurotrophin receptor), and its interaction with proapoptotic ligands pro-nerve growth factor and amyloid-beta peptide." S "Alzheimer's disease, a paradigm proteopathy, is accompanied by the formation of two distinct aggregates, amyloid fibrils and paired helical filaments (PHFs). (...) We find that PHFs are comprised of alpha-helices." S |
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| Affected Region | Dysfunctions |
| Temporal lobe | "Medial temporal lobe atrophy (MTA) is an early sign of Alzheimer's disease (AD)." S |
| Hippocampus | "Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD." S |
| Dentate Gyrus |
"Dysregulation of BDNF synthesis and Arc function, specifically within the dentate gyrus,
is linked to behavioral symptoms and cognitive deficits in animal models of depression and Alzheimer's
disease."
S "Neurogenesis has been reported to be increased in the dentate gyrus of patients with Alzheimer disease, but it is not known whether the newly generated neurons differentiate into mature neurons. In this study, the expression of the mature neuronal marker high molecular weight microtubule-associated protein (MAP) isoforms MAP2a and b was found to be dramatically decreased in Alzheimer disease dentate gyrus, as determined by immunohistochemistry and in situ hybridization. The total MAP2, including expression of the immature neuronal marker, the MAP2c isoform, was less affected. These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased." S |
| Posterior Cingulate Cortex | "The results demonstrate why a severe and persistent inability both to understand and produce meaningful speech in the absence of an impairment to process linguistic forms is usually only observed after bilateral, and particularly anterior, destruction of the temporal lobes, and emphasize the importance of retrosplenial/posterior cingulate cortex, an area known to be affected early in the course of Alzheimer's disease, in the processing of memories during communication." S |
| Mammillary body | "Study findings are consistent with previous research showing volume decreases of the fornix and mammillary bodies in AD, and provide new data on the relative preservation of these structures in preclinical disease stages. Results suggest that atrophy of the fornix and mammillary bodies becomes apparent at the point of conversion from MCI to AD." S |
| Fornix | "We conclude that FA (fractional anisotropy) is decreased in the white matter in preclinical and even presymptomatic FAD (familial Alzheimer's disease) mutation carriers, particularly in the late-myelinating tracts connecting limbic structures. Decreased FA in of the columns of the fornix is particularly robust in early FAD and may provide a biomarker for early disease in sporadic Alzheimer's disease." S |
| Superior colliculus | "The frequent presence of grossly anticipatory saccades may reflect dysfunction of fixation mechanisms possibly involving projections from frontal lobe to superior colliculus." S |
| Black substance | "Preliminary studies have shown an increase in iron accumulation in the substantia nigra but not in the hippocampus in patients with Parkinson disease without dementia and the reverse in patients with Alzheimer disease (AD) and no parkinsonism. (...) The development of parkinsonism during the course of AD appears to be associated with the accumulation of iron, which in turn may contribute to the pathogenesis of neurologic decline." S |
| Locus caeruleus | "(...) another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD." S |
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