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Molecular pathogenesis of Alzheimer’s disease – today’s biomarkers

Neurodegenerative disorders cause great suffering for patients as well as relatives and place an immense economic burden to our health care system. With increasing life expectancy these problems are likely to become even more pronounced in the future. Today symptomatic treatments are used, but these can not halt nor reverse the disease processes. A common denominator of neurodegenerative disorders affecting elderly is the pathological accumulation of proteins with an altered conformation, either within or between neurons of the affected brain regions. In Alzheimer’s disease, the most common form of dementia, amyloid-beta (Abeta) peptides deposit in the parenchyma and vessel walls of the brain. Due to its hydrophobic nature Abeta monomers gradually aggregate and form larger soluble molecular species (oligomers/protofibrils), which eventually result in insoluble fibrils and senile plaques. Alzheimer’s disease shares some pathological features with both Dementia with Lewy bodies and frontotemporal dementia. Intraneuronal aggregates of alfa-synuclein protein (Lewy bodies) are found in many Alzheimer brains and in all cases with Dementia with Lewy bodies. The latter is the second most common dementia disorder and often difficult to clinically separate from Alzheimer’s disease. The neurofibrillary tangle is another intracellular protein inclusion seen in brains of patients with Alzheimer’s disease and frontotemporal dementia, which is the third most common neurodegenerative disorder.

Thus these biomarkers are fairly good to discriminate early disease state for differential diagnosis, but they are neither suitable to follow disease progression nor to monitor drug intervention. Therefore there is a need for good biomarkers that reflect the disease process and correlate with the severity of the disease. Ideally, to be useful for monitoring pharmacological interventions, it should also have a wide dynamic range, mirror the response to drugs and reflect the functional state of the patient with respect to the disease.

 

Thematic area leader

Prof. Lars Lannfelt

PARTNERS
Uppsala Berzelii Technology Centre for Neurodiagnostics | Email info@berzelii.uu.se