Title:The Brainstem Tau Cytoskeletal Pathology of Alzheimer’s Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance
Volume: 13
Issue: 10
Author(s): Udo Rüb, Katharina Stratmann, Helmut Heinsen, Domenico Del Turco, Kay Seidel, Wilfred den Dunnen and Horst-Werner Korf
Affiliation:
Keywords:
Alzheimer’s disease, brainstem, cytoskeletal pathology, pathoanatomy, tau.
Abstract: The human brainstem is involved in the regulation of the sleep/waking
cycle and normal sleep architectonics and is crucial for the performance of a variety
of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive
and somatosensory functions. It harbors the origins of the ascending dopaminergic,
cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending
serotonergic system. In contrast to the cerebral cortex the affection of the
brainstem in Alzheimer’s disease (AD) by the neurofibrillary or tau cytoskeletal
pathology was recognized only approximately fourty years ago in initial brainstem
studies. Detailed pathoanatomical investigations of silver stained or tau immunostained
brainstem tissue sections revealed nerve cell loss and prominent ADrelated
cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia
nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology
was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior
olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus
of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of
pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular
reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations
in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood
disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations,
dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated
pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades,
dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in
some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction
and brain spread of the AD-related cytoskeletal pathology.
