The speed of progression of Alzheimer's disease-related neurofibrillary changes is unknown. One reason for this is the impossibility to histopathologically follow-up one and the same individual over decades of their life. The present approach takes advantage of a recently introduced classification system which allows for a ranking of Alzheimer's disease-related neurofibrillary changes into six stages [Braak and Braak Acta Neuropath (1991)82, 239–259] and analyses a staged sample of 887 brains obtained from routine autopsy. It sets out to interpret these cross-sectional data in dynamic longitudinal terms, in order to estimate the rate of passing through the various stages. The time needed to attain respective stages of pathology for 5% of a given cumulative sample is determined. The resulting fifth centiles are a measure of the average rate by which the disease-related changes progress assuming that the underlying stages represent a sequence of events and do not independently emerge. Advancing age and the prevalence of Alzheimer's disease-related changes of a given stage show a nonlinear positive correlation with only slight acceleration above the age of 65 years. Statistically, it takes at least 16 years from stage I to stage II, about 14 years pass by from stage II to III, 13 years from stage III to IV and five years from stage IV to V (= Alzheimer's disease) for 5% of a given cumulative sample.Thus, the deep roots of Alzheimer's disease-related neurofibrillary changes can be traced about 50 years back and may even extend into adolescence. The unveiling of the duration of the shift between selected stages provides a powerful tool for epidemiological studies. A possible risk factor should shorten this period whereas beneficial influences would result in a delayed shift even if the considered cohort dies “too early” for the full development of Alzheimer's disease.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.