Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-ß plaques.

Massive deposition of amyloid ß peptides (Aß) as senile plaques (SP) characterizes the brain pathology of Alzheimer's disease (AD). SPs exhibit a variety of morphologies, although little is known about the SP components that determine their morphology. Collagenous Alzheimer amyloid plaque component (CLAC) is one of the major non-Aß proteinaceous components of SP amyloid in AD brains. Here we show that overexpression of CLAC precursor (CLAC-P) in the brains of APP transgenic mice results in a significant remodeling of amyloid pathology, i.e., reduction in diffuse-type amyloid plaques and an increase in compact plaques laden with thioflavin S-positive amyloid cores. In vivo microdialysis revealed a significant decrease in Aß in the brain interstitial fluid of CLAC-P/APP double transgenic mice compared with APP transgenic mice. These findings implicate CLAC in the compaction of Aß in amyloid plaques and the brain dynamics of Aß.

Chronic optogenetic activation augments aß pathology in a mouse model of Alzheimer disease.

In vivo experimental evidence indicates that acute neuronal activation increases Aß release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Aß pathology remain unclear. To address this issue, we adopted optogenetics and transduced stabilized step-function opsin, a channelrhodopsin engineered to elicit a long-lasting neuronal hyperexcitability, into the hippocampal perforant pathway of APP transgenic mice. In vivo microdialysis revealed a ∼24% increase in the hippocampal interstitial fluid Aß42 levels immediately after acute light activation. Five months of chronic optogenetic stimulation increased Aß burden specifically in the projection area of the perforant pathway (i.e., outer molecular layer of the dentate gyrus) of the stimulated side by ∼2.5-fold compared with that in the contralateral side. Epileptic seizures were observed during the course of chronic stimulation, which might have partly contributed to the Aß pathology. These findings implicate functional abnormalities of specific neuronal circuitry in Aß pathology and Alzheimer disease.

Object relations in adolescence: a comparison of normal and inpatient adolescents.

AIMS: We aimed to study the development of object relations in adolescents and their correlation with their mothers' defense styles in inpatient and normal adolescents. METHODS: We administered the Thematic Apperception Test to adolescents in the adolescent unit (junior high, n = 16; senior high, n = 22) and normal controls (junior high, n = 16; senior high, n = 16). Results were analyzed using the Complexity of Representations Scale (CRS). We administered the Defense Style Questionnaire (DSQ(40)) to the subjects' mothers (patients, n = 38; controls, n = 32) to determine whether adolescents' CRS scores correlated with mothers' DSQ scores. RESULTS: There was a nearly significant interaction for group-by-school-year for the children's CRS scores. In the control group, senior high school students' scores (mean [SD] = 3.52 [0.49]) were significantly higher (F [1,66] = 12.3, P = 0.001) than those of junior high school students' (mean [SD] = 3.03 [0.31]). In the patient group, no significant difference was observed between senior high and junior high. For mothers' DSQ(40), mature defense scores were significantly higher in the control group than in the patient group (mean [SD] = 10.8 [1.89] vs 9.35 [1.40] in junior high, and 11.8 [1.67] vs 9.36 [1.81] in senior high, F [1,66] = 22.1, P < 0.001, two-way ANOVA). A significant, positive correlation (r = 0.37, P = 0.04) was observed between the mothers' mature defense and the children's CRS scores in the control group only. CONCLUSIONS: Whatever diagnoses are provided, the problems of adolescents with non-psychotic pathologies are related to the arrest of object relations development. A patient's mother cannot employ mature mechanisms to alleviate signals of anxiety sent by her child.