TY - JOUR
T1 - Structural (dys)connectivity associates with cholinergic cell density in Alzheimer's disease
AU - Lin, Chen Pei
AU - Frigerio, Irene
AU - Boon, Baayla D. C.
AU - Zhou, Zihan
AU - Rozemuller, Annemieke J. M.
AU - Bouwman, Femke H.
AU - Schoonheim, Menno M.
AU - van de Berg, Wilma D. J.
AU - Jonkman, Laura E.
N1 - Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Cognitive deficits in Alzheimer's disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-β and phosphorylated-tau pathology at autopsy. To understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer's disease, we used a combined post-mortem in situ MRI and histopathology approach. A total of 19 Alzheimer's disease (10 amnestic and nine non-amnestic) and nine non-neurological control donors underwent 3 T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-β, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer's disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. Exploratory post hoc subgroup analyses indicated that cholinergic cell density could be associated with cortical tract alterations in amnestic Alzheimer's disease donors only. Our study illustrates that in Alzheimer's disease, cholinergic degeneration in the nucleus basalis of Meynert may contribute to damaged cortical projections, specifically to the temporal lobe, leading to cognitive deterioration.
AB - Cognitive deficits in Alzheimer's disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-β and phosphorylated-tau pathology at autopsy. To understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer's disease, we used a combined post-mortem in situ MRI and histopathology approach. A total of 19 Alzheimer's disease (10 amnestic and nine non-amnestic) and nine non-neurological control donors underwent 3 T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-β, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer's disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. Exploratory post hoc subgroup analyses indicated that cholinergic cell density could be associated with cortical tract alterations in amnestic Alzheimer's disease donors only. Our study illustrates that in Alzheimer's disease, cholinergic degeneration in the nucleus basalis of Meynert may contribute to damaged cortical projections, specifically to the temporal lobe, leading to cognitive deterioration.
KW - Alzheimer’s disease
KW - cholinergic neurons
KW - histopathology
KW - nucleus basalis of Meynert
KW - post-mortem diffusion MRI
UR - http://www.scopus.com/inward/record.url?scp=85137135096&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/brain/awac093
DO - https://doi.org/10.1093/brain/awac093
M3 - Article
C2 - 35259207
SN - 0006-8950
VL - 145
SP - 2869
EP - 2881
JO - Brain
JF - Brain
IS - 8
ER -