Alzheimer's Disease Starts in Early Adulthood
H. Braak, E. Braak
Department of Anatomy, J.W. Goethe University, Theodor Stern Kai 7, D-60590, Frankfurt, Germany
Alzheimer's disease involves multiple neuronal systems and results from changes in the neuronal cytoskeleton which develop in only a few susceptible neuronal types. Initial alterations of the cerebral cortex develop in the transentorhinal region, located in anterior portions of the parahippocampal gyrus of the temporal lobe. The changes then invade other portions of the cerebral cortex and specific sets of subcortical nuclei. Examination of large numbers of non-selected cases obtained at autopsy demonstrates that the changes - even in small number - cannot be regarded as normal concomitants of brain aging. Rather, the first appearance of tangle-bearing nerve cells signals the beginning of the illness and represents part of its preclinical phase. Many cases show particularly early development of the cytoskeletal alterations, some of which start between the ages of twenty and thirty. Advanced age thus is not a prerequisite for the development of Alzheimer's disease. The mean of stages in the evolution of the neurofibrillary pathology increases with age. Accordingly, the disease is an age-related, but not an age-dependent brain disorder. An extended period of time elapses between the beginning of neuropathologically verifiable lesions and the appearance of initial clinical symptoms. Little is known about the conditions required for a particularly early appearance of the cytoskeletal changes in certain individuals. Once initiated, the destructive process underlying Alzheimer's disease progresses immutably,
and neither remission nor recovery is observed. Whether the destructive process is manifested clinically depends only on whether the life span of an affected individual allows its expression.