Research reportEarly involvement of the tegmentopontine reticular nucleus during the evolution of Alzheimer’s disease-related cytoskeletal pathology
Introduction
Clinically, Alzheimer’s disease (AD) is characterized by a complex constellation of symptoms, including the late manifestation of disturbances in memory and language functions, decline in intellectual capabilities, impairment of visuospatial skills, and changes in sleeping/waking cycles [13], [31]. In addition, AD patients display oculomotor dysfunctions, such as hypometrie of horizontal saccades and decelerated smooth pursuits [11], [12], [19], [22], [27], [36].
The neuropathological hallmarks of AD are intraneuronal cytoskeletal alterations and the extracellular deposition of the tegmentopontine reticular nucleus β-amyloid protein [6], [7], [30]. The gradual amassment of an abnormal tau protein that is immunoreactive with the antibody AT8 eventually leads to the formation of argyrophilic neurofibrillary tangles (NFTs) in nerve cell somata and neuropil threads (NTs) in nerve cell processes [3], [6], [7]. The gradual expansion of the AD-related neurofibrillary changes within the cerebral cortex follows a stereotypical sequence that can been divided into six stages (NFT/NT stages I–VI), which reflect the preclinical clinical and clinical course of AD [6], [8], [23], [24].
The tegmentopontine reticular nucleus (nucleus of Bechterew) is integrated into oculomotor circuits that regulate horizontal saccades and smooth pursuit movements of the eyes (Fig. 1) [10], [16], [18], [26], [32], [35]. The present study demonstrates an early and progressive involvement of this brain stem nucleus during the evolution of the AD-related cytoskeletal pathology.
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Materials and methods
The brains of 27 individuals (16 females, mean age 80.1±6.8 years; and 11 males, mean age 78.7±8.7 years) were obtained post mortem and fixed by immersion in a 4% aqueous, unbuffered formaldehyde solution. The brain stems were severed at the level of the inferior colliculus perpendicularly to the brain stem axis of Meynert, embedded in polyethylene glycol (PEG 1000, Merck, Germany), and cut into uninterrupted series of 100-μm frontal sections [6]. A serial collection consisting of the first,
Anatomical remarks
The tegmentopontine reticular nucleus (nucleus of Bechterew) is a bilaterally symmetrical nucleus located close to the midline of the pontine tegmentum (Fig. 2A, B). It is bordered dorsally by the caudal portion of the dorsal raphe nucleus and ventrally by the pontine nuclear gray (Fig. 2B) [4], [29], [33]. Its supero- and inferolateral portions form wing-like processes that abut on the medial longitudinal fascicle and the medial lemniscus (Fig. 2B).
Sections stained for Nissl material and
Discussion
The present study points to the early involvement in AD of the tegmentopontine reticular nucleus (nucleus of Bechterew) during the evolution of the AD-related cytoskeletal pathology, going beyond the findings of two earlier studies [25], [34]. According to our evidence, the development of the cytoskeletal pathology in this pontine nucleus begins already at NFT/NT stage I and progresses linearly with the NFT/NT staging sequence I–VI, thereby reflecting with reasonable accuracy the preclinical as
Acknowledgements
This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG BR 634/7-2). The skillful assistance of A. Biczysko and M. Lazar (processing of tissue sections, immunocytochemistry) and I. Szász (graphics) is appreciatively acknowledged.
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