Introduction
in AD
Pyroglutamate-modified Aß
in AD
Axonal degene-
ration in AD
mouse models
Intraneuronal Aß
and neuron loss
in AD
Alzheimer’s disease (AD) is a neurodegenerative disease that, in its most common form, is found in people over age 65. Approximately 24 million people worldwide have dementia of which the majority (~60%) is due to AD.
Clinical signs of Alzheimer’s disease are characterized by progressive cognitive deterioration, together with declining activities of daily living and by neuropsychiatric symptoms or behavioral changes. It is the most common type of dementia. Plaques which contain misfolded peptides called amyloid beta (Aß) are formed in the brain many years before the clinical signs of Alzheimer's are observed. Together, these plaques and neurofibrillary tangles form the pathological hallmarks of the disease. Many AD cases in addition develop cortical synucleopathy. These features can only be discovered at autopsy and help to confirm the clinical diagnosis. Medications can help reduce the symptoms of the disease, but they cannot change the course of the underlying pathology.
The ultimate cause of Alzheimer’s is unknown. Genetic factors are clearly indicated as evidenced by dominant mutations in three different genes have been identified that account for the small number of cases of familial, early-onset AD. For the more common form of late onset AD, ApoE is the only clearly established susceptibility gene. All four genes can contain mutations or variants that confer increased risk for AD, but account for only 30% of the genetic picture of AD. These four genes have in common the fact that mutations in each lead to the excessive accumulation in the brain of Aß, the main component of the senile plaques that litter the brains of AD patients.
We are primarily interested in studying mechanisms that modulate AD pathology using transgenic mouse models, which have been proven to be valuable tools to elucidate major disease mechanisms. Our research team has long-standing experience in validating AD mouse models on the basis of an integrative and interdisciplinary approach. Main focus is to understand the mechanisms of neuron death in vivo and the consequences on neuronal network assessed by behavioral tests.
Distribution of human Aß peptides(green) in neurons and amyloid plaques in mouse brain.
Distribution of humanAß peptides (blue)
and APP (brown)
in neurons and amyloid plaques
in mouse brain.
