Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS.
Apical dendrites of Betz cells are important sites for the integration of cortical input, however their health has not been fully assessed in ALS patients. We investigated the primary motor cortices isolated from post-mortem normal control subjects, patients with familial ALS (fALS), sporadic ALS (sALS), ALS with frontotemporal dementia (FTD-ALS), and Alzheimer's disease (AD), and found profound apical dendrite degeneration of Betz cells in both fALS and sALS, as well as FTD-ALS patients. In contrast, Betz cells of AD patients and normal controls retain cellular integrity in the motor cortex, and CA1 pyramidal neurons show abnormalities predominantly within their soma, rather than the apical dendrite. In line with extensive vacuolation and cytoarchitectural disintegration, the numbers of synapses were also significantly reduced only in ALS patients. Our findings indicate apical dendrite degeneration as a novel cellular pathology that distinguishes ALS and further support the importance of cortical dysfunction for disease pathology.
Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
Barış
B
Genç
Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
Javier H
JH
Jara
Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.
Amiko K B
AK
Lagrimas
Department of Pathology, University of Chicago Medical Center, Chicago, IL, 60637, USA.
Peter
P
Pytel
Department of Neurology, University of Chicago Medical Center, Chicago, IL, 60637, USA.
Raymond P
RP
Roos
Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, IL, 60611, USA.
M Marsel
MM
Mesulam
Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, IL, 60611, USA.
Changiz
C
Geula
Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, IL, 60611, USA.
Eileen H
EH
Bigio
Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA.|Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, IL, 60611, USA.|Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
P Hande
PH
Özdinler
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000473:pathology*; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009044:Motor Cortex / Q000166:cytology / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D019636:Neurodegenerative Diseases; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology