The premotor region essential for rapid vertical eye movements shows early involvement in Alzheimer's disease-related cytoskeletal pathology

Abstract

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 and β-amyloid deposits in this nucleus were examined in 30 autopsy cases and compared to the involvement of three associated nuclei — Edinger–Westphal nucleus, nucleus of Darkschewitsch and interstitial nucleus of Cajal. The riMLF displays slight cytoskeletal alterations already in the early stages in the development of the cortical cytoskeletal pathology (cortical NFT/NT-stages I–II, representing the preclinical phase of AD). In the cortical NFT/NT-stages III–IV (i.e. incipient phase of AD), the cytoskeletal pathology 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 correlates significantly with the cortical NFT/NT-stages I–VI that reflect the clinical course of AD. Isolated β-amyloid deposits appear in the riMLF for the first time in the final β-amyloid stage. In the Edinger–Westphal nucleus, in the nucleus of Darkschewitsch and most markedly in the interstitial nucleus of Cajal, the pathological changes were significantly less severe than those in the riMLF. In the event that the cytoskeletal pathology impairs the function of the premotor neurons of the riMLF, one would predict a progressive slowing of vertical saccades corresponding to the advancing cortical NFT/NT-stages.