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Enhanced Tau Aggregation in the Presence of Amyloid β.Am J Pathol. 2017 Jul; 187(7):1601-1612.AJ
Abstract
Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but with different topological and temporal patterns. Whether these two lesions are independent or pathobiologically related is uncertain. For example, amyloid deposition in the neocortex precedes the spread of tau neurofibrillary tangles from the limbic areas to the cortex. We examined the aggregation properties of tau isolated from human cases with early tau pathology (Braak II) with and without plaques. Using a well-established HEK cell biosensor assay, we show that tau from cases with plaques has an enhanced ability to induce tau aggregates compared to tau from cases without plaques. To further explore this effect, we combined mice carrying the APP/PS1 transgene array that develop plaques with rTg4510 mice carrying the P301L mutant human tau transgene that develop extensive tau pathology with age. The resulting APP/PS1-rTg4510 mice had a threefold increase in tau seeding activity over the rTg4510 strain, without change in tau production or extracellular release. Surprisingly, this effect was observed before overt amyloid deposition. The enhancement of tau aggregation was also apparent by an increase in histological measures of tau pathology in young APP/PS1-rTg4510 mice and an increase in high-molecular-weight tau. Overall, these data provide evidence that amyloid β acts to enhance tau pathology by increasing the formation of tau species capable of seeding new aggregates.
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MeSH
Pub Type(s)
Journal Article
Language
eng
PubMed ID
28500862
Citation
Bennett, Rachel E., et al. "Enhanced Tau Aggregation in the Presence of Amyloid Β." The American Journal of Pathology, vol. 187, no. 7, 2017, pp. 1601-1612.
Bennett RE, DeVos SL, Dujardin S, et al. Enhanced Tau Aggregation in the Presence of Amyloid β. Am J Pathol. 2017;187(7):1601-1612.
Bennett, R. E., DeVos, S. L., Dujardin, S., Corjuc, B., Gor, R., Gonzalez, J., Roe, A. D., Frosch, M. P., Pitstick, R., Carlson, G. A., & Hyman, B. T. (2017). Enhanced Tau Aggregation in the Presence of Amyloid β. The American Journal of Pathology, 187(7), 1601-1612. https://doi.org/10.1016/j.ajpath.2017.03.011
Bennett RE, et al. Enhanced Tau Aggregation in the Presence of Amyloid Β. Am J Pathol. 2017;187(7):1601-1612. PubMed PMID: 28500862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Enhanced Tau Aggregation in the Presence of Amyloid β.
AU - Bennett,Rachel E,
AU - DeVos,Sarah L,
AU - Dujardin,Simon,
AU - Corjuc,Bianca,
AU - Gor,Rucha,
AU - Gonzalez,Jose,
AU - Roe,Allyson D,
AU - Frosch,Matthew P,
AU - Pitstick,Rose,
AU - Carlson,George A,
AU - Hyman,Bradley T,
Y1 - 2017/05/10/
PY - 2017/01/18/received
PY - 2017/03/01/revised
PY - 2017/03/22/accepted
PY - 2017/5/14/pubmed
PY - 2017/10/14/medline
PY - 2017/5/14/entrez
SP - 1601
EP - 1612
JF - The American journal of pathology
JO - Am J Pathol
VL - 187
IS - 7
N2 - Amyloid plaques and neurofibrillary tangles co-occur in Alzheimer disease, but with different topological and temporal patterns. Whether these two lesions are independent or pathobiologically related is uncertain. For example, amyloid deposition in the neocortex precedes the spread of tau neurofibrillary tangles from the limbic areas to the cortex. We examined the aggregation properties of tau isolated from human cases with early tau pathology (Braak II) with and without plaques. Using a well-established HEK cell biosensor assay, we show that tau from cases with plaques has an enhanced ability to induce tau aggregates compared to tau from cases without plaques. To further explore this effect, we combined mice carrying the APP/PS1 transgene array that develop plaques with rTg4510 mice carrying the P301L mutant human tau transgene that develop extensive tau pathology with age. The resulting APP/PS1-rTg4510 mice had a threefold increase in tau seeding activity over the rTg4510 strain, without change in tau production or extracellular release. Surprisingly, this effect was observed before overt amyloid deposition. The enhancement of tau aggregation was also apparent by an increase in histological measures of tau pathology in young APP/PS1-rTg4510 mice and an increase in high-molecular-weight tau. Overall, these data provide evidence that amyloid β acts to enhance tau pathology by increasing the formation of tau species capable of seeding new aggregates.
SN - 1525-2191
UR - https://www.unboundmedicine.com/medline/citation/28500862/Enhanced_Tau_Aggregation_in_the_Presence_of_Amyloid_β_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(17)30080-9
DB - PRIME
DP - Unbound Medicine
ER -
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