Neurobiology of aging
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Neurobiology of aging · Nov 2013
Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer's disease leads to enhanced cognitive impairment despite of a reduction in amyloid deposition.
Alzheimer's disease (AD) is characterized by amyloid-β deposition in amyloid plaques, neurofibrillary tangles, inflammation, neuronal loss, and cognitive deficits. Cannabinoids display neuromodulatory and neuroprotective effects and affect memory acquisition. Here, we studied the impact of cannabinoid receptor type 1 (CB1) deficiency on the development of AD pathology by breeding amyloid precursor protein (APP) Swedish mutant mice (APP23), an AD animal model, with CB1-deficient mice. ⋯ Nevertheless, compared to APP23 mice with an intact CB1, APP23/CB1(-/-) mice showed impaired learning and memory deficits. These data argue against a direct correlation of amyloid plaque load with cognitive abilities in this AD mouse model lacking CB1. Furthermore, the findings indicate that CB1 deficiency can worsen AD-related cognitive deficits and support a potential role of CB1 as a pharmacologic target.
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Neurobiology of aging · Oct 2013
TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia.
Homozygous mutations in TREM2 have been recently identified by exome sequencing in families presenting with frontotemporal dementia (FTD)-like phenotype. No study has evaluated the exact frequency of TREM2 mutations in cohorts of FTD patients so far. We sequenced TREM2 in 175 patients with pure FTD, mostly French, to test whether mutations could be implicated in the pathogenesis of the disease. ⋯ We did not identify the polymorphism p. R47H (rs75932628), strongly associated with an increased risk of developing Alzheimer's disease. We conclude that TREM2 mutations are extremely rare in patients with pure FTD, although further investigation in larger populations is needed.
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Neurobiology of aging · Oct 2013
Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome.
It is known that individuals with Down syndrome develop Alzheimer's disease with an early age at onset, although associated genetic risk factors have not been widely studied. We tested whether genes that increase the risk of late-onset Alzheimer's disease influence the age at onset in Down syndrome using genome-wide association data for age at onset of dementia in a small sample of individuals (N = 67) with Down syndrome. We tested for association with loci previously associated with Alzheimer's disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer's disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014). As dementia in people with Down syndrome is relatively understudied, we make all of these data publicly available to encourage further analyses of the problem of Alzheimer's disease in Down syndrome.
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Neurobiology of aging · Sep 2013
Cerebral microbleeds are related to subjective cognitive failures: the RUN DMC study.
Cerebral small vessel disease (SVD), including white matter lesions (WML) and lacunar infarcts, is related to objective cognitive impairment but also to subjective cognitive failures (SCF). SCF have reported to be an early predictor of dementia. Cerebral microbleeds (MB) are another manifestation of SVD and have been related to cognitive impairment, but the role of MB in SCF has never been studied. ⋯ In conclusion, MB are related to SCF independent of co-existing WML and lacunar infarcts, especially in those with good objective cognitive performance. These results suggest that MB are associated with the earliest manifestations of cognitive impairment. MB may help us to understand the role of the ever-expanding spectrum of SVD in cognitive impairment.
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Neurobiology of aging · Aug 2013
Nerve growth factor retrieves neuropeptide Y and cholinergic immunoreactivity in the nucleus accumbens of old rats.
The nucleus accumbens (NAc) contains high levels of neuropeptide Y (NPY), which is involved in the regulation of functions and behaviors that deteriorate with aging. We sought to determine if aging alters NPY expression in this nucleus and, in the affirmative, if those changes are attributable to the cholinergic innervation of the NAc. The total number and the somatic volume of NPY- and choline acetyltransferase-immunoreactive neurons, and the density of cholinergic varicosities were estimated in the NAc of adult (6 months old) and aged (24 months old) rats. ⋯ The number of cholinergic neurons and the density of the cholinergic varicosities were unchanged, but their somas were hypertrophied. Nerve growth factor administration to aged rats further increased the volume of cholinergic neurons, augmented the density of the cholinergic varicosities, and reversed the age-related decrease in the number of NPY neurons. Our data show that the age-related changes in NPY levels in the NAc cannot be solely ascribed to the cholinergic innervation of the nucleus.