The DOI matches its Crossref record; 111 of the 111 references it cites were found in a registry or an index; none of the 24 sources its claims cite is checked for support yet.
Pathogenic protein seeding in alzheimer disease and other neurodegenerative disorders
Open accessAbstract
The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β‐amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from small oligomers to the characteristic lesions that are visible by optical microscopy, such as senile plaques and neurofibrillary tangles. Pathologic similarities with prion disease suggest that the formation and spread of these proteinaceous lesions might involve a common molecular mechanism—corruptive protein templating. Experimentally, cerebral β‐amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds. The amyloid‐inducing agent probably is Aβ itself, in a conformation generated most effectively in the living brain. Once initiated, Aβ lesions proliferate within and among brain regions. The induction process is governed by the structural and biochemical nature of the Aβ seed, as well as the attributes of the host, reminiscent of pathogenically variant prion strains. The concept of prionlike induction and spreading of pathogenic proteins recently has been expanded to include aggregates of tau, α‐synuclein, huntingtin, superoxide dismutase‐1, and TDP‐43, which characterize such human neurodegenerative disorders as frontotemporal lobar degeneration, Parkinson/Lewy body disease, Huntington disease, and amyotrophic lateral sclerosis. Our recent finding that the most effective Aβ seeds are small and soluble intensifies the search in bodily fluids for misfolded protein seeds that are upstream in the proteopathic cascade, and thus could serve as predictive diagnostics and the targets of early, mechanism‐based interventions. Establishing the clinical implications of corruptive protein templating will require further mechanistic and epidemiologic investigations. However, the theory that many chronic neurodegenerative diseases can originate and progress via the seeded corruption of misfolded proteins has the potential to unify experimental and translational approaches to these increasingly prevalent disorders. Ann Neurol 2011;70:532–540
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Written from the paper’s full text.
TL;DR
This review argues that many neurodegenerative proteopathies, including Alzheimer’s disease, progress by prion-like corruptive protein templating, in which misfolded protein seeds induce and spread aggregation of Aβ, tau, α-synuclein, and other proteins. It synthesizes experimental seeding evidence and discusses implications for biomarkers, therapeutics, and possible iatrogenic transmission, while noting that clinical implications remain uncertain.
Key findings
- In Alzheimer’s disease, Aβ aggregation is implicated as an early trigger; cerebral Aβ deposition precedes clinical symptoms by a decade or more, and tauopathy correlates strongly with cognitive decline. Oligomeric Aβ, ranging from dimers to dodecamers or larger, may be more deleterious than histologically obvious plaques and cerebral amyloid angiopathy.
- Cerebral β-amyloidosis can be experimentally induced in APP-transgenic mice by intracerebral infusion of brain extracts containing minute amounts of aggregated Aβ. Evidence includes that seeding requires aggregated human-sequence Aβ, is impeded by anti-Aβ immunodepletion, is ineffective in non-transgenic mice, mirrors the donor deposit phenotype, and is abrogated by formic acid denaturation.
- The most potent Aβ seeds appear to be small and soluble, including proteinase K-sensitive species in the 100,000×g soluble fraction; sonication enhances seeding. In contrast, aggregated synthetic Aβ has not significantly induced cerebral Aβ deposition in APP-transgenic mice.
- Tau tangles can be exogenously induced by brain extract containing abnormal tau filaments in Alz17 mice, with time- and region-dependent spread; prion-like propagation has also been implicated for α-synuclein, SOD1, TDP-43, and polyglutamine aggregates. Human prion disease transmission has occurred in fewer than 700 known cases.
Methods
- Narrative review; no new primary data are reported. It synthesizes human neuropathology, genetics, imaging, and transgenic mouse/cell-culture seeding experiments.
- The main analysis is a conceptual synthesis of evidence for corruptive protein templating across Alzheimer’s disease, prion disease, tauopathies, synucleinopathies, amyotrophic lateral sclerosis/frontotemporal lobar degeneration, and Huntington’s disease.
- No systematic search strategy, meta-analysis, or quantitative pooling is described.
Limitations
- Stated: many questions remain, clinical implications are uncertain, and much research on this phenomenon is fragmentary. The paper also states that there is no direct evidence linking non-prion neurodegenerative diseases to seeds arising outside the central nervous system or taken up from the environment.
- Stated: final evidence is lacking that in vivo tau induction occurs via prion-like corruptive templating rather than, for example, activation of a signaling cascade; the mode of cell-to-cell transfer of aggregates is unclear. Transmission of non-prion proteopathies by tainted instruments is a theoretical possibility not demonstrated in humans.
- Evident: as a narrative review, it does not provide systematic search criteria, quantitative synthesis, or primary experimental validation, and some cited findings are described as in press or not fully detailed.
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Claims the paper makes
0 of 24 cited sources checked · 0 supported · 0 flagged
In the paper
“Our recent finding that the most effective Aβ seeds are small and soluble”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Abstract
What the sources say
- Not checked yetcites [54] Langer F Eisele YS Fritschi S Staufenbiel M Walker LC Jucker M Soluble Aβ seeds are potent inducers of cerebral β-amyloid deposition J Neuroscience 2011 in press PMC3229270 21994365 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Using a paradigm similar to in vivo Aβ-seeding, neurofibrillary (tau) tangles can be exogenously induced by the intracerebral infusion of brain extract containing abnormal tau filaments into mice bearing a human tau transgene63.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Induction and spread of tau filaments in experimental animals
What the sources say
- Not checked yetcites [63] Clavaguera F Bolmont T Crowther RA Transmission and spreading of tauopathy in transgenic mouse brain Nat Cell Biol 2009 11 909 13 19503072 PMC2726961 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The seeded proliferation of misfolded proteins, a concept that arose and evolved in the prion field, holds considerable explanatory power for the pathogenesis of many of the neurodegenerative diseases that afflict our burgeoning elderly population.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While the transmission of non-prion proteopathies by tainted instruments thus is a theoretical possibility, proof of such a phenomenon (which could be obscured by a protracted incubation period) has not been demonstrated in humans.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Clinical, Practical and Theoretical Implications
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Experimentally, β-amyloid induction can be triggered in transgenic mice by intracerebrally implanted stainless steel wires coated with minute amounts of brain extract rich in aggregated Aβ52 (Fig 2).”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Clinical, Practical and Theoretical Implications
What the sources say
- Not checked yetcites [52] Eisele YS Bolmont T Heikenwalder M Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation Proc Natl Acad Sci U S A 2009 106 12926 31 19622727 PMC2722323 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Once initiated, Aβ lesions proliferate within and among brain regions.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“the (slight) risk of prion transmission by instruments used on patients with undiagnosed prion disease106”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Clinical, Practical and Theoretical Implications
What the sources say
- Not checked yetcites [106] Ward HJ Everington D Croes EA Sporadic Creutzfeldt-Jakob disease and surgery: a case-control study using community controls Neurology 2002 59 543 8 12196646 source
Strength:plain· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Experimentally, cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Abstract
What the sources say
- Not checked yetcites [49] Kane MD Lipinski WJ Callahan MJ Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice J Neurosci 2000 20 3606 11 10804202 PMC6772682 source
- Not checked yetcites [50] Walker LC Callahan MJ Bian F Durham RA Roher AE Lipinski WJ Exogenous induction of cerebral beta-amyloidosis in betaAPP-transgenic mice Peptides 2002 23 1241 7 12128081 source
- Not checked yetcites [51] Meyer-Luehmann M Coomaraswamy J Bolmont T Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host Science 2006 313 1781 4 16990547 source
- Not checked yetcites [52] Eisele YS Bolmont T Heikenwalder M Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation Proc Natl Acad Sci U S A 2009 106 12926 31 19622727 PMC2722323 source
- Not checked yetcites [53] Watts JC Giles K Grillo SK Lemus A DeArmond SJ Prusiner SB Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer’s disease Proc Natl Acad Sci U S A 2011 108 2528 33 21262831 PMC3038719 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In cell culture, however, the prion-like propagation of α-synuclein lesions has been demonstrated80, 81”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Induction and spread of protein aggregates linked to other neurodegenerative diseases
What the sources say
- Not checked yetcites [80] Desplats P Lee HJ Bae EJ Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein Proc Natl Acad Sci U S A 2009 106 13010 5 19651612 PMC2722313 source
- Not checked yetcites [81] Hansen C Angot E Bergstrom AL alpha-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells J Clin Invest 2011 121 715 25 21245577 PMC3026723 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The induction and proliferation of proteinaceous aggregates by corruptive protein templating appears to be a common feature of multiple, clinically diverse disorders, although many questions remain to be addressed (Table 1).”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Clinical, Practical and Theoretical Implications
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Findings from transgenic mouse and cell culture models of protein seeding are representative of the pathogenic process in human neurodegenerative diseases.
- Probably not a substantial claim. 2
- It may state two separate claims as one. 1
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The theoretical framework underlying this paradigm recently has expanded to include an extraordinary array of neurological and systemic disorders.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Conclusion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the clinical implications remain uncertain”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Conclusion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“In AD, cerebral β-amyloid deposition begins in humans at least a decade prior to the onset of cognitive decline, and hence is an early and predictive indicator of the disease4.”
§ Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders > Clinical, Practical and Theoretical Implications
What the sources say
- Not checked yetcites [4] Holtzman DM Morris JC Goate AM Alzheimer’s disease: the challenge of the second century Sci Transl Med 2011 3 77sr1 21471435 PMC3130546
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Findings from transgenic mouse and cell culture models of protein seeding are representative of the pathogenic process in human neurodegenerative diseases.
“Establishing the clinical implications of corruptive protein templating will require further mechanistic and epidemiologic investigations.”
The paper relies on this without support.
Cerebral proteopathies are growing in prevalence.
“the growing prevalence of cerebral proteopathies necessitates a comprehensive quest”
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In the citing paper
“A synapse-centred hypothesis also does not preclude the spreading hypothesis [34, 66], which could be either a downstream pathological event or a potential trigger of Tau-related excitotoxicity and synaptic failure.”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [66]
In the citing paper
“The fact that the amyloid tap turns itself off before clinical changes appreciably manifest, we feel, also argues against the idea that Aβ perpetuates itself in a prion-like fashion [261].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [261]
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
RetractedNeuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 3×
“Whereas the degree of tauopathy correlates strongly with cognitive decline in AD 6-8 , genetic, pathologic and biochemical evidence implicates the aggregation of A β as a critical, early trigger in the chain of events that leads to tauopathy, neuronal dysfunction and dementia 9 .”
BackgroundThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · cited 1×
“In the brain, the a-synuclein–rich lesions that typify Lewy body disease/Parkinson disease first arise in the lower brainstem (notably the dorsal motor nucleus of the vagus nerve), and in the anterior olfactory nucleus and the olfactory bulb; they subsequently appear in a predictable sequence in mesencephalic and neoc…”
BackgroundSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
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 · cited 2×
“Crosssectional autopsy studies indicate that b-amyloid (Ab) plaques (A) first appear in the neocortex, followed by the allocortex and finally subcortical regions.(21) In the brain, neurofibrillary tangles (B) occur first in the locus coeruleus and transentorhinal area and then spread to the amygdala and interconnected…”
BackgroundMethodSynapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
Buckner, R. L., Snyder, A. Z., Shannon, B. J., LaRossa, G., Sachs, R., Fotenos, A. F., Sheline, Y. I., Klunk, W. E., Mathis, C. A., Morris, J. C., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2177-05.2005 · Cited by 2,140
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Items 601–625 of 625
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Olabiyi, A. A., & Adeniyi, P. A. (2025) · Advances in neurotoxicology · doi:10.1016/bs.ant.2025.04.009
Kim, H., Kim, S., Cho, B., Shin, J., & Kim, J. (2022) · Figshare · doi:10.6084/m9.figshare.21400433
Takaichi, Y., Chambers, J. K., Takahashi, K., Soeda, Y., Koike, R., Katsumata, E., Kita, C., Matsuda, F., Haritani, M., Takashima, A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13545644
Ehrenhofer‐Murray, A. E. (2025) · Springer eBooks · doi:10.1007/978-3-662-70328-1_14
Sepulveda-Diaz, J. E. (2013) · theses.fr (ABES) · doi:10.70675/56c42bcbz41dfz432bzbb78z77110b373285
Etude préclinique et clinique de la phase précoce de la maladie d'Alzheimer
Epelbaum, S. (2015) · theses.fr (ABES) · doi:10.70675/ea81e5c2z5032z4474z9f96z59f62125a629
Vandenberghe, M. E. (2015) · theses.fr (ABES) · doi:10.70675/c7b69fb2z393bz46fcz9000z5a9c52ba79c4 · Cited by 1
Eysert, F. (2019) · theses.fr (ABES) · doi:10.70675/cde90ae3z11f1z43e2z8031zae68eac45ec8
“Enfin, le dernier stade dit « isocortical » est atteint lorsque l’isocortex est totalement affecté (Braak & Braak, 1991; Jucker & Walker, 2011, 2013) (Figure 3).”
BackgroundCharacterisation of non-covalent PrP assemblies
Bohl, J. (2019) · theses.fr (ABES) · doi:10.70675/2a939bf5z2532z4002z8f02zb15095f2657e
Oscillatory processes during the aggregation and the fragmentation of amyloid fibrils
Mezache, M. (2019) · theses.fr (ABES) · doi:10.70675/49713145z3079z463bzbba2z53ff9386b599
Lam, S. (2021) · theses.fr (ABES) · doi:10.70675/60b353ffz56fcz41a2z9e53zf0d9ac078167 · Cited by 1
Sirajo, M. U., Rukevwe, O., Mukhtar, A. I., Abdullahi, N. M., Taniyohwo, E. M., Oyem, J. C., & Badamasi, I. M. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1754364
“AD models, on the other hand, have commonly been developed through genetic manipulation to overexpress mutant forms of proteins such as beta-amyloid (A β ) or tau (57).”
Physiological and pathological functions of TAF15 in neurodegenerative diseases and cancers
Liu, C., Meng, L., & Zhang, Z. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.04.066
TDP‐43 Aggregation: The Healthy‐Toxic Balance of the Prion‐Like Domain
Zangrando, L., Buratti, E., & Paron, F. (2026) · Advanced Science · doi:10.1002/advs.76119 · Cited by 1
“Regarding Alzheimer’s disease (AD), β -amyloid represents one of the best-characterized examples of non-PrP proteins undergoing prion-like seeded aggregation and self-propagation in vivo, thereby extending the prion paradigm to broader neurodegenerative proteinopathies [ 173, 176, 177 ].”
Conformational bifurcation of tau R3–R4 oligomers underlies fibril polymorphism
Zhang, T., Dai, L., Ma, Y., Xu, S., Liu, X., Zhao, M., Li, W., Wang, J., & Liu, Y. (2026) · Biophysical Journal · doi:10.1016/j.bpj.2026.07.020
Xie, Y., Chong-Teik, L., Lam, X.-J., Cheah, P.-S., Ling, K., & Huang, T. (2026) · PLoS ONE · doi:10.1371/journal.pone.0354882
“Notably, the aggregation mechanisms of these misfolded proteins share prion-like properties, whereby aberrant proteins can induce conformational changes in their normally folded counterparts, facilitating pathological propagation across neuronal circuits [7,8].”
Duran-Aniotz, C. A., Morales, R., Moreno‐González, I., & Soto, C. A. (2013) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-35491-5_6
“and HD (Brundin et al. 2010; Frost and Diamond 2010; Jucker and Walker 2011; Soto 2012b).”
BackgroundANÁLISE CITOGENÉTICA COMO BIOINDICADOR PARA PACIENTES COM DIAGNÓSTICO SUGESTIVO DE ALZHEIMER
Ramos, I. P., & Negrão (2013) · Americanae (AECID Library)
Therapeutic Effects of Hydrogen on Different Diseases
Qian, L., Shen, J., & Sun, X. (2015) · Springer eBooks · doi:10.1007/978-94-017-9691-0_6
Metadata
- Authors
- Jucker, M., & Walker, L. C.
- Affiliations
- Emory University (US)
- Corresponding author
- Jucker, Mathias
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2011-10
- Volume
- 70
- Issue
- 4
- Pages
- 532-540
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3203752
- OpenAlex
- W2018852249
- Semantic Scholar
- a083431598aa8300a06d560a5e6377c2d187348a
- Cited by
- 622
- References
- 111
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 16 · 2023: 26 · 2022: 30 · 2021: 25 · 2020: 45 · 2019: 47 · 2018: 39 · 2017: 47 · 2016: 46 · 2015: 63 · 2014: 58 · 2013: 85 · 2012: 57
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DZNE Pub (submittedVersion)
- Funders
- U.S. Public Health Service (NCRR RR-00165)
- National Institute on Aging (P01AG026423, P50AG025688)
- National Center for Research Resources (P51RR000165)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, tau protein, prion-like propagation, protein aggregation, neurodegenerative diseases, frontotemporal lobar degeneration, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, alpha-synuclein, TDP-43, superoxide dismutase 1, huntingtin, amyloid seeding, diagnostic biomarkers
- MeSH terms
- Alzheimer Disease, Animals, DNA-Binding Proteins, Humans, Prions, Proteins, Amyloid beta-Peptides, tau Proteins, Neurodegenerative Diseases
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