阿尔茨海默氏病研究进展(英文)最新文献

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

Chronic neuroinflammation is thought to play an etiological role in Alzheimer's disease (AD), which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatiotemporal link between neuritic and amyloid pathology, with the obligatory enzyme for β-amyloid (Aβ) production, namely β-secretase-1 (BACE1), is overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aβ in these genetically modified animals. Here we explored the occurrence of the AD-like axonal and dendritic pathology in adult rat brain affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated the ipsilateral hippocampal lysates in the LPS treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased β-amyloid precursor protein and Aβ antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.