Cited by 581Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Amyloid-β-independent regulators of tau pathology in Alzheimer disease

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van der Kant, Rik, Goldstein, Lawrence S. B., Ossenkoppele, Rik·2020·Nature reviews. Neuroscience

DOI 10.1038/s41583-019-0240-3

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Abstract

The global epidemic of Alzheimer disease (AD) is worsening, and no approved treatment can revert or arrest progression of this disease. AD pathology is characterized by the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain. Genetic data, as well as autopsy and neuroimaging studies in patients with AD, indicate that Aβ plaque deposition precedes cortical tau pathology. Because Aβ accumulation has been considered the initial insult that drives both the accumulation of tau pathology and tau-mediated neurodegeneration in AD, the development of AD therapeutics has focused mostly on removing Aβ from the brain. However, striking preclinical evidence from AD mouse models and patient-derived human induced pluripotent stem cell models indicates that tau pathology can progress independently of Aβ accumulation and arises downstream of genetic risk factors for AD and aberrant metabolic pathways. This Review outlines novel insights from preclinical research that implicate apolipoprotein E, the endocytic system, cholesterol metabolism and microglial activation as Aβ-independent regulators of tau pathology. These factors are discussed in the context of emerging findings from clinical pathology, functional neuroimaging and other approaches in humans. Finally, we discuss the implications of these new insights for current Aβ-targeted strategies and highlight the emergence of novel therapeutic strategies that target processes upstream of both Aβ and tau.

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Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979

Show all 216 references

Research works printed but not linked: 7

Kemp, A. Update on phase III clinical trials of lanabecestat for Alzheimer’s disease. AstraZeneca https://www.astrazeneca.com/media-centre/press-releases/2018/update-on-phase-iii-clinical-trials-of-lanabecestat-for-alzheimers-disease-12062018.html (2018).
Jansen, W. J. et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA 313, 1924–1938 (2015). This large meta-analysis provides prevalence estimates of Aβ positivity in cognitively normal persons and patients with MCI. · DOI · Paper page
Cho, H. et al. Progressive tau accumulation in Alzheimer’s disease: two-year follow-up study. J. Nucl. Med. 60, 1611–1621 (2019). · DOI · Paper page
Hutter-Paier, B. et al. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer’s disease. Neuron 44, 227–238 (2004). This study shows that cholesteryl esters can drive accumulation of Aβ pathology in AD mice and that ACAT inhibitors have potential utility in the treatment of AD. · DOI · Paper page
Mecozzi, V. J. et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nat. Chem. Biol. 10, 443–449 (2014). This revolutionary biochemical study uses in silico screening to discover a small molecule that is capable of stabilizing the retromer complex. · DOI · Paper page
Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523–527 (2017). This elegant mouse study shows that the ApoE*4 genotype affects tau pathology in the absence of Aβ pathology. · DOI · Paper page
Santacruz, K. et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309, 476–481 (2005). This is the first study to show that reducing tau expression in tau transgenic mice can rescue neuronal loss and behavioural deficits, even when extensive neurofibrillary tangles are already present. · DOI · Paper page

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Rubinski, A., Franzmeier, N., Dewenter, A., Luan, Y., Smith, R. A., Strandberg, O. T., Ossenkoppele, R., Dichgans, M., Hansson, O., Ewers, M., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01074-9 · Cited by 41
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Wiesman, A. I., Murman, D. L., May, P. E., Schantell, M. D., Losh, R. A., Johnson, H. J., Willett, M. P., Eastman, J. A., Christopher‐Hayes, N. J., Knott, N. L., et al. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12200 · Cited by 33
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Authors: van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R.
Affiliations: University of California San Diego (US)
Lund University (SE)
ORCID: van der Kant, Rik
Goldstein, Lawrence S. B.
Ossenkoppele, Rik
Venue: Nature reviews. Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2019-11-28
Volume: 21
Issue: 1
Pages: 21-35
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/s41583-019-0240-3
OpenAlex: W2989855650
Cited by: 580
References: 216
Citations by year: 2026: 57 · 2025: 89 · 2024: 93 · 2023: 89 · 2022: 95 · 2021: 95 · 2020: 61
FWCI: 7.39
Type: journal article
Language: en
Open access: green
research.vu.nl
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
VU Research Portal (publishedVersion, other-oa)
Lund University Publications (Lund University) (submittedVersion)
Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: National Institute on Aging (RF1AG048083)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, tau pathology, amyloid-beta, apolipoprotein E, cholesterol metabolism, microglial activation, induced pluripotent stem cell models, mouse model
MeSH terms: Alzheimer Disease, Animals, Apolipoproteins E, Cholesterol, Endocytosis, Humans, Amyloid beta-Peptides, tau Proteins, Microglia, Plaque, Amyloid

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Amyloid-β-independent regulators of tau pathology in Alzheimer disease

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