Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD.

Methodology/principal Findings: The double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment.

Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease.

To investigate the role of the Wnt inhibitor Dickkopf-1 (DKK-1) in the pathophysiology of neurodegenerative diseases, we analysed DKK-1 expression and localization in transgenic mouse models expressing familial Alzheimer's disease mutations and a frontotemporal dementia mutation. A significant increase of DKK-1 expression was found in the diseased brain areas of all transgenic lines, where it co-localized with hyperphosphorylated tau-bearing neurons. In TgCRND8 mice, DKK-1 immunoreactivity was detected in neurons surrounding amyloid deposits and within the choline acetyltransferase-positive neurons of the basal forebrain.

Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease.

Clioquinol (CQ) is a "metal protein attenuating compound" that crosses the blood-brain barrier and binds, with high affinity, copper(II) and zinc(II), two metal ions critically involved in amyloid-beta aggregation and toxicity. CQ was recently proposed for the treatment of Alzheimer's disease, but controversial data have been reported so far concerning its real therapeutic advantages. We describe here results of chronic CQ treatment in the TgCRND8 mouse model of Alzheimer's disease.

Increased expression of the oligopeptidase THOP1 is a neuroprotective response to Abeta toxicity.

In a comprehensive proteomics study aiming at the identification of proteins associated with amyloid-beta (Abeta)-mediated toxicity in cultured cortical neurons, we have identified Thimet oligopeptidase (THOP1). Functional modulation of THOP1 levels in primary cortical neurons demonstrated that its overexpression was neuroprotective against Abeta toxicity, while RNAi knockdown made neurons more vulnerable to amyloid peptide. In the TgCRND8 transgenic mouse model of amyloid plaque deposition, an age-dependent increase of THOP1 expression was found in brain tissue, where it co-localized with Abeta plaques.

Combined treatment with atorvastatin and minocycline suppresses severity of EAE.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of the central nervous system (CNS). An approach to improve MS treatment is to identify a rational combination of new medications or existing therapies that impact different aspects of the disease process. Statins are effective in the treatment of MS animal models and are promising candidates for future treatment.

Abnormal processing of tau in the brain of aged TgCRND8 mice.

Amyloid plaques and neurofibrillary tangles are the main histopathological hallmarks of Alzheimer's disease (AD). In the neocortex and hippocampus of aged TgCRND8 mice, tau is hyperphosphorylated at different sites recognized by PHF-1, AT100, AT8 and CP13 antibodies. Phospho-SAPK/JNK levels were increased in the tg mouse brain, where activated SAPK/JNK co-localizes with PHF-1-positive cells.