P110 - AB DIMERS IMPAIR ADULT HIPPOCAMPAL NEUROGENESIS AND AFFECT CIRCADIAN RHYTHMS (ID 2001)

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Abstract

Aims

AD represents the most common cause of dementia in elderly manifested with impairments in cognitive and emotional functions as well as sleep disturbances. Although aggregation of Amyloid-β (Aβ) and neurofibrillary tangles are hallmarks of AD neuropathology, Aß oligomers have recently been considered as the most neurotoxic species leading to cognitive and non-cognitive manifestations. Here, we analyze their effect on hippocampal adult neurogenesis, known to contribute to neuronal plasticity, and on the circadian system that entrains rhythms in behavior and physiology to the 24h solar day.

Methods

tgDimer mice express Aß dimers in a soluble state without plaques formation or neuroinflammation, therefore, allows to dissect the pure effect of soluble Aß dimers in AD pathology. Moreover, they show memory deficits, thus, represent a model for early AD.

We investigated adult hippocampal neurogenesis using markers for proliferation (BrdU) and neuroblast (DCX) via immunohistochemistry. Integrity of the circadian system was analyzed by rhythmic locomotor activity, recorded using infrared detectors, and expression of the core clock gene Per1 in the suprachiasmatic nucleus (SCN), the central circadian rhythm generator, by quantitative PCR in tgDimer mice.

Results

We found a significant reduction of BrdU+ neural progenitor cells and DCX+ neuroblasts in tgDimer mice as compared to WT mice. Furthermore, tgDimer mice exhibit higher locomotor activity during early light/rest phase, reminiscent of sundowning behavior in AD patients, and increased sensitivity to chronodisruption, in addition to decreased Per1 expression in the SCN.

Conclusions

Our results show that soluble Aß dimers impair adult hippocampal neurogenesis and affect the circadian system.

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P109 - TRANSDIFFERENTIATION OF REACTIVE ASTROCYTES INTO NEURONS IN A RAT MODEL OF ALZHEIMER’S DISEASE (ID 741)

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