Lysosomes robustly accumulate within axonal swellings at Alzheimer's disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cul...

The formation of extracellular amyloid plaques is a common patho-biochemical event underlying several debilitating human conditions, including Alzheimer's disease (AD). Considerable evidence implies that AD damage arises primarily from small oligomeric amyloid forms of Abeta peptide, but the precise mechanism of pathogenicity remains to be established. Using a cell culture system that reproduci...

While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fib...

Alzheimer's disease (AD) is the most common cause of dementia. A fundamental feature of AD is brain region-specific deposition of extracellular amyloid plaques principally comprised of the amyloid-β (Aβ) peptide. Using mouse models of cerebral Aβ deposition, we examined molecular, cellular and systems-level mechanisms that regulate brain region-specific Aβ accumulation and aggregation. Parallel...

Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaqu...

Alzheimer's disease (AD) is characterized by a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. Nonsteroidal anti-inflammatory drug (NSAID) treatment reduces AD risk, slows disease progression, and reduces microglial activation; however, the basis of these effects is unknown. We report that treatment of 11-month-old Tg2576 mice overexpressing huma...

Amyloid plaques are a key pathological hallmark of Alzheimer's disease (AD). The detection of amyloid plaques in the brain is important for the diagnosis of AD, as well as for following potential amyloid targeting therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (µMRI) in AD transgenic mice, where ...

Amyloid imaging has been clinically approved for measuring β amyloid plaque load in patients being evaluated for Alzheimer's disease or other causes of cognitive decline. Here we explore a multidimensional approach to cognitive decline, where we situate amyloid plaque burden among a number of other relevant dimensions, such as aging, volume loss, other proteinopathies such as TDP43 and Lewy bod...

Feasibility of immunotherapy for Alzheimer’s disease has been postulated, and numerous strategies of active and passive immunization have been applied in animals and humans. This article summarizes accumulated knowledge in clinical trials and animal experiments, and foresees the future perspective. Clinical trials have clearly shown that clearance of senile plaque amyloid is insufficient for im...

Alzheimer's desease is the most common age-related neurodegenerative disorder, and cognitive problems such as defects in learning and memory are of its symptoms.  Among the factors involved in the pathogenesis of the disease are biochemical disorders in protein production, oxidative stress, decreased acetylcholine secretion and inflammation of the brain tissue. Extra-neuronal accumulation ...