Alzheimer’s disease (AD) is now the fifth leading cause of death in people over 65 years old. The prevalence of AD is increasing rapidly as the world population ages; data show that the incidence increases exponentially after the age of 65, with more than 40% of those aged over 85 now affected. According to a 2012 WHO report, nearly 36 million people globally are living with dementia, around two thirds of whom have AD, and this number is predicted to triple by 2050. The 18th World Alzheimer’s day on the 21st of September emphasized the need to reduce the stigma of dementia and make communities ‘dementia-friendly’. While these aims are laudable, the pressing need is for very early diagnosis and timely effective treatment if health services are not to be totally overwhelmed by the escalating numbers of AD patients needing care.
Two major abnormalities, clearly visible at autopsy, are present in abundance in the brains of AD patients, namely beta-amyloid plaques (Aβ) and neurofibrillary tangles (tau protein). However these lesions are not very evident using even advanced neuroimaging techniques, and the disease is most frequently diagnosed by psychological tests and rule-out of other causes of neurodegeneration, so that many early cases remain undiagnosed. Clinical research to allow early diagnosis has mainly focused on fluid biomarkers, and genetic risk factors and markers. Stanford University School of Medicine, USA, has been concentrating on the former approach with the aim of eventually developing a simple blood test that would confirm the onset of AD several years before clinical symptoms were apparent. Initially researchers compared signalling proteins from the blood of patients with and without AD. Their more recent work uses animal models to compare neurons from the hippocampal formation, which are very vulnerable and die in the early stages of AD, with neurons which are not affected until the late stages of the disease. Several labs based in Europe are concentrating on finding cerebrospinal fluid markers present in the early stages of AD, such as total tau, phosphorylated tau and the 42 amino acid form of Aβ, which would allow early specific and sensitive diagnosis. The search for genetic markers has demonstrated that the genes APOE and PICALM consistently affect Aβ.
Early diagnosis, however, must be followed by effective treatment. Currently cholinesterase inhibitors and NMDA receptor antagonists are used to alleviate symptoms but are not curative. Sadly just before this year’s World Alzheimer’s day it was announced that two antibody drugs targetting Aβ, namely Bapineuzumab from Pfizer and Solanezumab from Eli Lilly, had proved to be no better than placebo in Phase III clinical trials. Last year the European Parliament called for dedicated plans to reduce the burden of AD; a new funding model to ensure that big pharma doesn’t withdraw from the AD challenge could be the most valuable strategy.