Alzheimer disease, a progressive neurodegenerative disorder of hitherto unknown etiology leading progressively to severe incapacity and death, has become the pandemic of the 21st century. On World Alzheimer Day, September 21, 2006, the 100th anniversary of the first description of the clinical and histological findings in this disorder by A. Alzheimer, was celebrated. This retrospective review of the most important events and advances in Alzheimer research presents its early history in which only clinical and histologic signs of this peculiar disease were described. Electron microscopy, quantitative morphology and modern biochemistry emerging in the second half of the 20th century opened a new era in dementia research with description of the ultrastructure and biochemistry of senile plaques and neurofibrillary tangles, the major disease markers of AD. Advances in the development of clinical, neuropathological, and neuroimaging criteria, modern instruments and algorithms in the diagnosis of the disorder followed, enabling long-term studies and more exact diagnosis of AD and related disorders. Landmark studies were the development of operational criteria for the post mortem diagnosis of AD based on semiquantitative assessment and developmental patterns of its major markers. Basic research gave insight into the molecular genetics and pathophysiology of AD, and, based on the biochemical findings, new pharmacological treatment options were opened. Recently, biological and other surrogate, in particular functional neuroimaging, markers allow an early detection of presymptomatic stages of AD, their risk factors and progression which, in the future, might be prevented or at least slowed by new therapeutic approaches. Since the etiology of AD is hitherto unknown, causative therapies are still not available. The paper discusses future research needs and challenges for developing new diagnostic strategies for early and accurate detection of neurodegenerative processes leading to dementia, better epidemiologic and gender data as well as more insights into the pathogenic cascade of AD and other dementing disorders which will depend on international networks and close cooperation between clinicians, neuroscientists, caregivers, public health institutions, and individual sponsors.
