Evolution of Alzheimer's disease-related cytoskeletal changes in the basalnucleus of Meynert

This study examines the evolution of Alzheimer's disease (AD)-related patho logy in a subcortical predilection site, the basal nucleus of Meynert (bnM) , which is a major source of cortical cholinergic innervation. Brains of 51 autopsy cases were studied using silver techniques and immunostaining for tau-associated neurofibrillary pathology and for amyloid beta protein (A be ta) deposits. All cases are classified according to a procedure permitting differentiation of six stages of AD-related neurofibrillary changes in the cerebral cortex. Initial cytoskeletal abnormalities in the bnM are already noted in stage I of cortical neurofibrillary changes. The gradual developme nt of the neurofibrillary pathology in the bnM parallels the progression of the AD-related stages in the cerebral cortex. A variety of morphologically distinguishable cytoskeletal alterations are observed in large nerve cells which predominate in the bnM. Based on these cellular alterations, a seque nce of cytoskeletal deterioration is proposed. Initially, the abnormal tau protein is distributed diffusely throughout the cell body and the neuronal processes. Subsequently, it aggregates to form a neurofibrillary tangle, wh ich appears as a spherical somatic inclusion. The cell processes gradually become fragmented. Finally the parent cell dies, leaving behind an extraneu ronal "ghost tangle". With regard to the cortical stages of AD-related neur ofibrillary changes, the initial forms of cytoskeletal changes in the bnM p redominate in the transentorhinal AD stages (I and II), while "ghost tangle s" preferentially occur in the neocortical stages (V and VI). The considera ble morphological diversity of cytoskeletal alterations is typical of stage s III and IV. These results indicate that individual neurons of the bnM ent er the sequence of cytoskeletal deterioration at different times.