New developments in mild cognitive impairment and Alzheimer's disease.
OBJECTIVE
In this paper, we review current concepts of Alzheimer's disease, recent progress in diagnosis and treatment and important developments in our understanding of its pathogenesis with a focus on beta-amyloid both as culprit and therapeutic target.


RESULTS
The amyloid cascade hypothesis of Alzheimer's disease pathogenesis continues to predominate with evidence suggesting that small oligomeric forms of Abeta-42 rather than fibrils or senile plaques are the key pathological substrates. The concept of mild cognitive impairment continues to be refined to define better those patients who will progress to Alzheimer's disease. Structural and functional imaging techniques and cerebrospinal fluid biomarkers are gaining acceptance as diagnostic markers of Alzheimer's disease, with a potentially exciting advance being the ability to image amyloid in vivo using novel positron emission tomography ligands. Whilst available treatments afford only symptomatic benefits, disease-modifying treatments may be within reach. Despite the halting of the first amyloid beta-vaccination trial due to adverse effects, amyloid immunotherapy continues to show promise, with new approaches already entering clinical trials. Other therapeutic strategies under investigation include inhibition of beta -and gamma-secretase, key enzymes implicated in Alzheimer's disease pathogenesis.


CONCLUSIONS
Current research demonstrates the potential for diagnostic strategies and disease modifying treatments to follow from an ever more detailed understanding of the molecular mechanisms underlying the pathogenesis of Alzheimer's disease.
Schott
Jonathan M
JM
Institute of Neurology, Dementia Research Centre, National Hospital for Neurology and Neurosurgery, London, UK.
Kennedy
Jonathan
J
Fox
Nick C
NC
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D003952:Diagnostic Imaging / Q000639:trends; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D011237:Predictive Value of Tests
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D053829:Amyloid Precursor Protein Secretases