Neurobiology of aging
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Neurobiology of aging · Sep 2014
Hippocampal subfield volumes at 7T in early Alzheimer's disease and normal aging.
We compared hippocampal subfield and entorhinal cortex (ERC) volumes between patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and controls without cognitive impairment. Additionally, we investigated the relation between age and hippocampal subfields and ERC in controls. We performed ultra-high field 0.7 mm(3) 7Tesla magnetic resonance imaging in 16 patients with amnestic MCI, 9 with AD, and 29 controls. ⋯ Older age was significantly associated with smaller CA1 and DG&CA4 volumes. In conclusion, almost all hippocampal subfields and ERC show volume reductions in patients with AD compared with controls and patients with MCI. Future, larger studies should determine which subfields are affected earliest in the disease process and what mechanisms underlie the volume loss.
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L-arginine is a semi-essential amino acid with a number of bioactive metabolites. Accumulating evidence suggests the implication of altered arginine metabolism in the pathogenesis of Alzheimer's disease (AD). ⋯ There were also AD- and age-related changes in the tissue concentrations of L-arginine and its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, γ-aminobutyric acid, and glutamine) in a metabolite- or region-specific manner. These findings demonstrate that arginine metabolism is dramatically altered in diverse regions of AD brains, thus meriting further investigation to understand its role in the pathogenesis and/or progression of the disease.
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Neurobiology of aging · Jul 2014
Maternal separation impairs long term-potentiation in CA1-CA3 synapses and hippocampal-dependent memory in old rats.
Exposure to chronic stress during the neonatal period is known to induce permanent long-term changes in the central nervous system and hipothalamic-pituitary-adrenal axis reactivity that are associated with increased levels of depression, anxiety, and cognitive impairments. In rodents, a validated model of early life stress is the maternal separation (MS) paradigm, which has been shown to have long-term consequences for the pups that span to adulthood. We hypothesized that the early life stress-associated effects could be exacerbated with aging, because it is often accompanied by cognitive decline. ⋯ We then investigated whether these differences are linked to impaired function of hippocampal neurons by recording hippocampal long-term potentiation from Schaffer collaterals/CA1 synapses. The magnitude of the hippocampal long-term potentiation induced by high-frequency stimulation was significantly lower in aged MS animals than in age-matched controls. These results substantiate the hypothesis that the neuronal and endocrine alterations induced by early-life stress are long lasting, and are able to exacerbate the mild age-associated deficits.
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TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p. R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). ⋯ Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p. S144G (rs3747742) as a potential driver of the meta-analysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD.
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Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. ⋯ DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease.