Tracing of temporo-entorhinal connections in the human brain: cognitively impaired argyrophilic grain disease cases show dendritic alterations but no axonal disconnection of temporo-entorhinal association neurons |
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Authors: | Dietmar Rudolf Thal Estibaliz Capetillo-Zarate Ralf A Galuske |
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Institution: | (1) Department of Pathology, Laboratory of Neuropathology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany;(2) Department of Neuropathology, University of Bonn, Bonn, Germany;(3) Department of Biology, Technical University Darmstadt, Darmstadt, Germany;(4) Present address: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA |
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Abstract: | Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often associated with mild to moderate Alzheimer’s disease
(AD)-related pathology. The development of dementia in AGD is associated with the extent of coexisting AD-related pathology.
Therefore, the question arises whether the degenerative changes in the neuronal network of demented AGD-patients represent
a distinct pattern or show similar changes of disconnection as considered for AD. We were able to apply DiI-tracing in two
human autopsy cases with mild AD-related pathology (controls), in one AD-patient, in one non-demented patient with advanced
AD-related pathology, and in three cognitively impaired AGD-patients. DiI-crystals were injected into the entorhinal cortex.
Pyramidal neurons of layers III and V of the adjacent temporal neocortex (area 35) were retrogradely marked with the tracer
and analyzed. The AD case did not exhibit any retrogradely labeled neurons in the temporal neocortex. In the non-demented
case with advanced AD-related pathology, the number of traced neurons was reduced as compared to that in the two controls
and in the three AGD cases. In contrast, all three cognitively impaired AGD cases exhibited labeled pyramidal neurons in area
35 in an almost similar number as in the controls. However, alterations in the dendritic tree were observed in the AGD cases.
These results show the existence of temporo-entorhinal connections in the adult human brain similar to those reported in animal
models. Furthermore, the present study based on seven cases is the first attempt to study changes in the neuronal network
in a human tauopathy with targeted axonal tracing techniques. Our findings in three cognitively impaired AGD cases suggest
that AGD-related dementia constitutes a distinct disorder with a characteristic pattern of degeneration in the neuronal network. |
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Keywords: | Alzheimer’ s disease Argyrophilic grain disease Tracing Association neurons Neuronal connectivity |
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