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Castillo-Carranza DL, Nilson AN, Van Skike CE, et al. Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies. Aging Dis. 2017;8(3):257-266doi: 10.14336/AD.2017.0112.
Castillo-Carranza, D. L., Nilson, A. N., Van Skike, C. E., Jahrling, J. B., Patel, K., Garach, P., Gerson, J. E., Sengupta, U., Abisambra, J., Nelson, P., Troncoso, J., Ungvari, Z., Galvan, V., & Kayed, R. (2017). Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies. Aging and disease, 8(3), 257-266. https://doi.org/10.14336/AD.2017.0112
Castillo-Carranza, Diana L, et al. "Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies." Aging and disease vol. 8,3 (2017): 257-266. doi: https://doi.org/10.14336/AD.2017.0112
Castillo-Carranza DL, Nilson AN, Van Skike CE, Jahrling JB, Patel K, Garach P, Gerson JE, Sengupta U, Abisambra J, Nelson P, Troncoso J, Ungvari Z, Galvan V, Kayed R. Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies. Aging Dis. 2017 May 02;8(3):257-266. doi: 10.14336/AD.2017.0112. eCollection 2017 May. PMID: 28580182; PMCID: PMC5440106.
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Aging Dis. 2017 May 02;8(3):257-266. doi: 10.14336/AD.2017.0112. eCollection 2017 May.

Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies.

Aging and disease

Diana L Castillo-Carranza, Ashley N Nilson, Candice E Van Skike, Jordan B Jahrling, Kishan Patel, Prajesh Garach, Julia E Gerson, Urmi Sengupta, Jose Abisambra, Peter Nelson, Juan Troncoso, Zoltan Ungvari, Veronica Galvan, Rakez Kayed

Affiliations

  1. 1Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA.
  2. 2Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  3. 4Department of Cellular and Integrative Physiology and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, TX 78245, USA.
  4. 5Sanders-Brown Center on Aging and Department of Physiology, University of Kentucky, Lexington, KY 40536, USA.
  5. 6Division of Neuropathology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
  6. 7Clinical and Neuropathology Core, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
  7. 8Department of Geriatric Medicine and Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma, OK 73104, USA.
  8. 3Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA.

PMID: 28580182 PMCID: PMC5440106 DOI: 10.14336/AD.2017.0112

Abstract

The importance of vascular contributions to cognitive impairment and dementia (VCID) associated with Alzheimer's disease (AD) and related neurodegenerative diseases is increasingly recognized, however, the underlying mechanisms remain obscure. There is growing evidence that in addition to Aβ deposition, accumulation of hyperphosphorylated oligomeric tau contributes significantly to AD etiology. Tau oligomers are toxic and it has been suggested that they propagate in a "prion-like" fashion, inducing endogenous tau misfolding in cells. Their role in VCID, however, is not yet understood. The present study was designed to determine the severity of vascular deposition of oligomeric tau in the brain in patients with AD and related tauopathies, including dementia with Lewy bodies (DLB) and progressive supranuclear palsy (PSP). Further, we examined a potential link between vascular deposition of fibrillar Aβ and that of tau oligomers in the Tg2576 mouse model. We found that tau oligomers accumulate in cerebral microvasculature of human patients with AD and PSP, in association with vascular endothelial and smooth muscle cells. Cerebrovascular deposition of tau oligomers was also found in DLB patients. We also show that tau oligomers accumulate in cerebral microvasculature of Tg2576 mice, partially in association with cerebrovascular Aβ deposits. Thus, our findings add to the growing evidence for multifaceted microvascular involvement in the pathogenesis of AD and other neurodegenerative diseases. Accumulation of tau oligomers may represent a potential novel mechanism by which functional and structural integrity of the cerebral microvessels is compromised.

Keywords: Alzheimer’s disease; brain vascular dysfunction; cerebrovascular dysfunction; cerebrovasculature; oligomers; tau; tauopathies

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