The Distribution of Phosphorylated Tau in Spinal Cords of Alzheimer's Disease and Non-Demented Individuals

Abnormal phosphorylation of the microtubule-associated protein tau develops in selected brain regions in normal aging and becomes widespread throughout the brain in Alzheimer's disease (AD). Braak and others have described the distribution of neurofibrillary tangles and deposition of abnormally phosphorylated tau (p-tau) and correlated this with the progressive cognitive dysfunction in AD. However, to date there have been no comprehensive studies examining abnormally phosphorylated tau deposition in the spinal cord as part of normal aging or AD. We investigated, using immunohistochemical methods, the presence of p-tau in the spinal cord of 46 cases with a clinicopathological diagnosis of AD as well as 37 non-demented aged (ND) individuals lacking any defined central nervous system-related clinicopathological diagnosis. We found the cervical cord segments to be the most frequently affected subdivision (96% AD versus 43% ND), followed by thoracic (69% AD versus 37% ND), lumbar (65% AD versus 27% ND), and sacral (53% AD versus 13% ND). The spinal cord was often affected at early-stage brain disease, with p-tau spinal cord immunoreactivity in 40% of subjects at Braak neurofibrillary stage I; however, there were no cases having spinal cord p-tau that did not have p-tau within the brain. As p-tau immunoreactivity is present within the spinal cords of ND as well as AD subjects, it is likely that the phosphorylation of spinal cord tau occurs in the preclinical stage of AD, prior to dementia. The presence of significant spinal cord p-tau-immunoreactive pathology has important implications for both the pathogenesis and clinical manifestations of AD.