The premotor region essential for vapid vertical eye movements shows earlyinvolvement in Alzheimer's disease-related cytoskeletal pathology

The rostral interstitial nucleus of the medial longitudinal fascicle (riMLF ) contains premotor neurons essential for the generation of rapid vertical eye movements. The Alzheimer's disease (AD)-related cytoskeletal changes an d beta -amyloid deposits in this nucleus were examined in 30 autopsy cases and compared to the involvement of three associated nuclei - Edinger-Westph al nucleus, nucleus of Darkschewitsch and interstitial nucleus of Cajal. Th e riMLF displays slight cytoskeletal alterations already in the early stage s in the development of the cortical cytoskeletal pathology (cortical NFT/N T-stages I-II, representing the preclinical phase of AD). In the cortical N FT/NT-stages III-IV (i.e. incipient phase of AD), the cytoskeletal patholog y in the riMLF is pronounced and in stages V-VI (i.e. clinical phase of AD) it is severe. The progression of the cytoskeletal pathology in the riMLF c orrelates significantly with the cortical NFT/NT-stages I-VI that reflect t he clinical course of AD. Isolated beta -amyloid deposits appear in the riM LF for the first time in the final beta -amyloid stage. In the Edinger-West phal nucleus, in the nucleus of Darkschewitsch and most markedly in the int erstitial nucleus of Cajal, the pathological changes were significantly les s severe than those in the riMLF. In the event that the cytoskeletal pathol ogy impairs the function of the premotor neurons of the riMLF, one would pr edict a progressive slowing of vertical saccades corresponding to the advan cing cortical NFT/NT-stages. (C) 2001 Elsevier Science Ltd. All rights rese rved.