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Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats.
J Alzheimers Dis. 2014; 42 Suppl 3:S205-15.JA

Abstract

BACKGROUND

Accumulation of amyloid-β (Aβ) and hyperphosphorylated tau (ptau) accompany cerebral small vessel disease (CSVD) in the aging brain and in Alzheimer's disease. CSVD is characterized by a heterogeneous spectrum of histopathological features possibly initiated by an endothelial dysfunction and blood-brain barrier (BBB) breakdown.

OBJECTIVE

We test the hypothesis that characteristic features of CSVD are associated with the accumulation of Aβ and ptau in non-transgenic spontaneously hypertensive stroke-prone rats (SHRSP).

METHODS

Amyloid-β protein precursor (AβPP) and tau were investigated by western blotting (n = 12 SHRSP, age 20 weeks). Lectin staining and plasma protein immunocytochemistry for BBB examination were performed in 38 SHRSP (age 12-44 weeks) and Aβ (n = 29) and ptau (n = 17) immunocytochemistry in 20-44 week-old SHRSP. We assessed the correlation between extracellular amyloid deposits and features of CSVD (n = 135, 12-44 weeks).

RESULTS

In 20 week-old SHRSP, cortical AβPP expression was significantly increased compared to Wistar controls but tau levels were unchanged. At ages of 20-44 weeks, SHRSP exhibited an age-dependent increase in extracellular Aβ. Ptau was observed in 26-44 week-old SHRSP. Distinct features of CSVD pathology developed from the age of 12 weeks on.

CONCLUSION

We demonstrate that in a hypertensive rat model that displays features of CSVD from 12 weeks, there is an age-dependent extracellular deposition of Aβ observed from 20 weeks onwards, increased AβPP expression at 20 weeks and ptau accumulation from 26 weeks on. This study suggests that CSVD associated with hypertension results in an age-related failure of Aβ clearance, increase in AβPP expression, and intraneuronal tau hyperphosphorylation.

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Authors+Show Affiliations

Schreiber S
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Drukarch B
Department of Anatomy and Neurosciences, Cellular Neuropharmacology group, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
Garz C
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
Niklass S
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
Stanaszek L
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Kropf S
Institute of Biometry and Medical Informatics, Otto-von-Guericke University, Magdeburg, Germany.
Bueche C
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Held F
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
Vielhaber S
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Attems J
Institute for Aging and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Reymann KG
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany.
Heinze HJ
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany.
Carare RO
Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Wilhelmus MM
Department of Anatomy and Neurosciences, Cellular Neuropharmacology group, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.

MeSH

AgingAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBlood PlateletsBlood ProteinsBlood-Brain BarrierBrainCerebral Small Vessel DiseasesDisease Models, AnimalDura MaterLectinsLongitudinal StudiesRatsRats, Inbred SHRRats, Wistartau Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24825568

Citation

Schreiber, Stefanie, et al. "Interplay Between Age, Cerebral Small Vessel Disease, Parenchymal Amyloid-β, and Tau Pathology: Longitudinal Studies in Hypertensive Stroke-prone Rats." Journal of Alzheimer's Disease : JAD, vol. 42 Suppl 3, 2014, pp. S205-15.
Schreiber S, Drukarch B, Garz C, et al. Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats. J Alzheimers Dis. 2014;42 Suppl 3:S205-15.
Schreiber, S., Drukarch, B., Garz, C., Niklass, S., Stanaszek, L., Kropf, S., Bueche, C., Held, F., Vielhaber, S., Attems, J., Reymann, K. G., Heinze, H. J., Carare, R. O., & Wilhelmus, M. M. (2014). Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats. Journal of Alzheimer's Disease : JAD, 42 Suppl 3, S205-15. https://doi.org/10.3233/JAD-132618
Schreiber S, et al. Interplay Between Age, Cerebral Small Vessel Disease, Parenchymal Amyloid-β, and Tau Pathology: Longitudinal Studies in Hypertensive Stroke-prone Rats. J Alzheimers Dis. 2014;42 Suppl 3:S205-15. PubMed PMID: 24825568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats. AU - Schreiber,Stefanie, AU - Drukarch,Benjamin, AU - Garz,Cornelia, AU - Niklass,Solveig, AU - Stanaszek,Luiza, AU - Kropf,Siegfried, AU - Bueche,Celine, AU - Held,Friederike, AU - Vielhaber,Stefan, AU - Attems,Johannes, AU - Reymann,Klaus G, AU - Heinze,Hans-Jochen, AU - Carare,Roxana O, AU - Wilhelmus,Micha M M, PY - 2014/5/15/entrez PY - 2014/5/16/pubmed PY - 2015/6/30/medline KW - Amyloid-β KW - amyloid-β protein precursor KW - cerebral small vessel disease KW - hyperphosphorylated tau KW - spontaneously hypertensive stroke-prone rats SP - S205 EP - 15 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 42 Suppl 3 N2 - BACKGROUND: Accumulation of amyloid-β (Aβ) and hyperphosphorylated tau (ptau) accompany cerebral small vessel disease (CSVD) in the aging brain and in Alzheimer's disease. CSVD is characterized by a heterogeneous spectrum of histopathological features possibly initiated by an endothelial dysfunction and blood-brain barrier (BBB) breakdown. OBJECTIVE: We test the hypothesis that characteristic features of CSVD are associated with the accumulation of Aβ and ptau in non-transgenic spontaneously hypertensive stroke-prone rats (SHRSP). METHODS: Amyloid-β protein precursor (AβPP) and tau were investigated by western blotting (n = 12 SHRSP, age 20 weeks). Lectin staining and plasma protein immunocytochemistry for BBB examination were performed in 38 SHRSP (age 12-44 weeks) and Aβ (n = 29) and ptau (n = 17) immunocytochemistry in 20-44 week-old SHRSP. We assessed the correlation between extracellular amyloid deposits and features of CSVD (n = 135, 12-44 weeks). RESULTS: In 20 week-old SHRSP, cortical AβPP expression was significantly increased compared to Wistar controls but tau levels were unchanged. At ages of 20-44 weeks, SHRSP exhibited an age-dependent increase in extracellular Aβ. Ptau was observed in 26-44 week-old SHRSP. Distinct features of CSVD pathology developed from the age of 12 weeks on. CONCLUSION: We demonstrate that in a hypertensive rat model that displays features of CSVD from 12 weeks, there is an age-dependent extracellular deposition of Aβ observed from 20 weeks onwards, increased AβPP expression at 20 weeks and ptau accumulation from 26 weeks on. This study suggests that CSVD associated with hypertension results in an age-related failure of Aβ clearance, increase in AβPP expression, and intraneuronal tau hyperphosphorylation. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24825568/Interplay_between_age_cerebral_small_vessel_disease_parenchymal_amyloid_β_and_tau_pathology:_longitudinal_studies_in_hypertensive_stroke_prone_rats_ DB - PRIME DP - Unbound Medicine ER -