Brain arteriolosclerosis

Brittney L Blevins; Harry V Vinters; Seth Love; Donna M Wilcock; Lea T Grinberg; Julie A Schneider; Rajesh N Kalaria; Yuriko Katsumata; Brian T Gold; Danny J J Wang; Samantha J Ma; Lincoln M P Shade; David W Fardo; Anika M S Hartz; Gregory A Jicha; Karin B Nelson; Shino D Magaki; Frederick A Schmitt; Merilee A Teylan; Eseosa T Ighodaro; Panhavuth Phe; Erin L Abner; Matthew D Cykowski; Linda J Van Eldik; Peter T Nelson

doi:10.1007/s00401-020-02235-6

Brain arteriolosclerosis

Brittney L Blevins, Harry V Vinters, Seth Love, Donna M Wilcock, Lea T Grinberg, Julie A Schneider, Rajesh N Kalaria, Yuriko Katsumata, Brian T Gold, Danny J J Wang, Samantha J Ma, Lincoln M P Shade, David W Fardo, Anika M S Hartz, Gregory A Jicha, Karin B Nelson, Shino D Magaki, Frederick A Schmitt, Merilee A Teylan, Eseosa T IghodaroPanhavuth Phe, Erin L Abner, Matthew D Cykowski, Linda J Van Eldik, Peter T Nelson

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Abstract

Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

Original language	English
Pages (from-to)	1-24
Number of pages	24
Journal	Acta Neuropathologica
Volume	141
Issue number	1
Early online date	24 Oct 2020
DOIs	https://doi.org/10.1007/s00401-020-02235-6
Publication status	Published - 1 Jan 2021

Bibliographical note

Funding Information:
We are very grateful to the research volunteers, their families, and clinicians, as well as the other researchers who made this work possible. This study was also supported by California Dept of Public Health Grant A20-2947-5001 and NIH Grants P30 AG028383, R01 AG057187, R01 AG039621, R01 AG055449, K24 AG053435, R56 AG057191, R01 HD064993, U54 NS100717, U01 AG016976, RF1 NS118584, and S10 OD023573. Additional support came from Medical Research Council (MRC, G0500247) and previous Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW), and Alzheimer’s Research (ARUK). The Newcastle Brain Tissue Resource is funded in part by a grant from the UK MRC (G0400074), by the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, and by a grant from the Alzheimer’s Society and ARUK as part of the Brains for Dementia Research Project. See Supplemental Acknowledgement for additional acknowledgments.

Publisher Copyright:
© 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Research Groups and Themes

Cerebrovascular and Dementia Research Group

Keywords

SVD
arteriosclerosis
cAVU
senescence
neuropathology
neuroimaging

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00401-020-02235-6

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Blevins, B. L., Vinters, H. V., Love, S., Wilcock, D. M., Grinberg, L. T., Schneider, J. A., Kalaria, R. N., Katsumata, Y., Gold, B. T., Wang, D. J. J., Ma, S. J., Shade, L. M. P., Fardo, D. W., Hartz, A. M. S., Jicha, G. A., Nelson, K. B., Magaki, S. D., Schmitt, F. A., Teylan, M. A., ... Nelson, P. T. (2021). Brain arteriolosclerosis. Acta Neuropathologica, 141(1), 1-24. https://doi.org/10.1007/s00401-020-02235-6

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abstract = "Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.",

keywords = "SVD, arteriosclerosis, cAVU, senescence, neuropathology, neuroimaging",

author = "Blevins, {Brittney L} and Vinters, {Harry V} and Seth Love and Wilcock, {Donna M} and Grinberg, {Lea T} and Schneider, {Julie A} and Kalaria, {Rajesh N} and Yuriko Katsumata and Gold, {Brian T} and Wang, {Danny J J} and Ma, {Samantha J} and Shade, {Lincoln M P} and Fardo, {David W} and Hartz, {Anika M S} and Jicha, {Gregory A} and Nelson, {Karin B} and Magaki, {Shino D} and Schmitt, {Frederick A} and Teylan, {Merilee A} and Ighodaro, {Eseosa T} and Panhavuth Phe and Abner, {Erin L} and Cykowski, {Matthew D} and {Van Eldik}, {Linda J} and Nelson, {Peter T}",

note = "Funding Information: We are very grateful to the research volunteers, their families, and clinicians, as well as the other researchers who made this work possible. This study was also supported by California Dept of Public Health Grant A20-2947-5001 and NIH Grants P30 AG028383, R01 AG057187, R01 AG039621, R01 AG055449, K24 AG053435, R56 AG057191, R01 HD064993, U54 NS100717, U01 AG016976, RF1 NS118584, and S10 OD023573. Additional support came from Medical Research Council (MRC, G0500247) and previous Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW), and Alzheimer{\textquoteright}s Research (ARUK). The Newcastle Brain Tissue Resource is funded in part by a grant from the UK MRC (G0400074), by the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, and by a grant from the Alzheimer{\textquoteright}s Society and ARUK as part of the Brains for Dementia Research Project. See Supplemental Acknowledgement for additional acknowledgments. Publisher Copyright: {\textcopyright} 2020, Springer-Verlag GmbH Germany, part of Springer Nature.",

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Blevins, BL, Vinters, HV, Love, S, Wilcock, DM, Grinberg, LT, Schneider, JA, Kalaria, RN, Katsumata, Y, Gold, BT, Wang, DJJ, Ma, SJ, Shade, LMP, Fardo, DW, Hartz, AMS, Jicha, GA, Nelson, KB, Magaki, SD, Schmitt, FA, Teylan, MA, Ighodaro, ET, Phe, P, Abner, EL, Cykowski, MD, Van Eldik, LJ & Nelson, PT 2021, 'Brain arteriolosclerosis', Acta Neuropathologica, vol. 141, no. 1, pp. 1-24. https://doi.org/10.1007/s00401-020-02235-6

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T1 - Brain arteriolosclerosis

AU - Blevins, Brittney L

AU - Vinters, Harry V

AU - Love, Seth

AU - Wilcock, Donna M

AU - Grinberg, Lea T

AU - Schneider, Julie A

AU - Kalaria, Rajesh N

AU - Katsumata, Yuriko

AU - Gold, Brian T

AU - Wang, Danny J J

AU - Ma, Samantha J

AU - Shade, Lincoln M P

AU - Fardo, David W

AU - Hartz, Anika M S

AU - Jicha, Gregory A

AU - Nelson, Karin B

AU - Magaki, Shino D

AU - Schmitt, Frederick A

AU - Teylan, Merilee A

AU - Ighodaro, Eseosa T

AU - Phe, Panhavuth

AU - Abner, Erin L

AU - Cykowski, Matthew D

AU - Van Eldik, Linda J

AU - Nelson, Peter T

N1 - Funding Information: We are very grateful to the research volunteers, their families, and clinicians, as well as the other researchers who made this work possible. This study was also supported by California Dept of Public Health Grant A20-2947-5001 and NIH Grants P30 AG028383, R01 AG057187, R01 AG039621, R01 AG055449, K24 AG053435, R56 AG057191, R01 HD064993, U54 NS100717, U01 AG016976, RF1 NS118584, and S10 OD023573. Additional support came from Medical Research Council (MRC, G0500247) and previous Newcastle Centre for Brain Ageing and Vitality (BBSRC, EPSRC, ESRC and MRC, LLHW), and Alzheimer’s Research (ARUK). The Newcastle Brain Tissue Resource is funded in part by a grant from the UK MRC (G0400074), by the Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, and by a grant from the Alzheimer’s Society and ARUK as part of the Brains for Dementia Research Project. See Supplemental Acknowledgement for additional acknowledgments. Publisher Copyright: © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

AB - Brain arteriolosclerosis (B-ASC), characterized by pathologic arteriolar wall thickening, is a common finding at autopsy in aged persons and is associated with cognitive impairment. Hypertension and diabetes are widely recognized as risk factors for B-ASC. Recent research indicates other and more complex risk factors and pathogenetic mechanisms. Here, we describe aspects of the unique architecture of brain arterioles, histomorphologic features of B-ASC, relevant neuroimaging findings, epidemiology and association with aging, established genetic risk factors, and the co-occurrence of B-ASC with other neuropathologic conditions such as Alzheimer's disease and limbic-predominant age-related TDP-43 encephalopathy (LATE). There may also be complex physiologic interactions between metabolic syndrome (e.g., hypertension and inflammation) and brain arteriolar pathology. Although there is no universally applied diagnostic methodology, several classification schemes and neuroimaging techniques are used to diagnose and categorize cerebral small vessel disease pathologies that include B-ASC, microinfarcts, microbleeds, lacunar infarcts, and cerebral amyloid angiopathy (CAA). In clinical-pathologic studies that factored in comorbid diseases, B-ASC was independently associated with impairments of global cognition, episodic memory, working memory, and perceptual speed, and has been linked to autonomic dysfunction and motor symptoms including parkinsonism. We conclude by discussing critical knowledge gaps related to B-ASC and suggest that there are probably subcategories of B-ASC that differ in pathogenesis. Observed in over 80% of autopsied individuals beyond 80 years of age, B-ASC is a complex and under-studied contributor to neurologic disability.

KW - SVD

KW - arteriosclerosis

KW - cAVU

KW - senescence

KW - neuropathology

KW - neuroimaging

U2 - 10.1007/s00401-020-02235-6

DO - 10.1007/s00401-020-02235-6

M3 - Review article (Academic Journal)

C2 - 33098484

SN - 0001-6322

VL - 141

SP - 1

EP - 24

JO - Acta Neuropathologica

JF - Acta Neuropathologica

IS - 1

ER -

Brain arteriolosclerosis

Abstract

Bibliographical note

Research Groups and Themes

Keywords

UN SDGs

Access to Document

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