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39/100

✓ Peer-reviewed alzhub usefulness score 39 out of 100. Lewy body dementia

Topic: Brain proteins, microglia and lab models

Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau's phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Fischer, D. L., Menard, M. A., Abdelaziz, O. Z., Kanaan, N. M., Cobbs, V. G., Kennedy, R., et al. (2025). Distinct subcellular localization of tau and alpha-synuclein in lewy body disease. Acta Neuropathologica Communications. https://doi.org/10.1186/s40478-024-01913-w

Vancouver

Fischer DL, Menard MA, Abdelaziz OZ, Kanaan NM, Cobbs VG, Kennedy R, et al. Distinct subcellular localization of tau and alpha-synuclein in lewy body disease. Acta Neuropathologica Communications. 2025. doi:10.1186/s40478-024-01913-w. PMID: 39838428.

BibTeX

@article{fischer2025-39838428,
  author  = {Fischer, D. Luke and Menard, Marissa A. and Abdelaziz, Omar Z. and Kanaan, Nicholas M. and Cobbs, Virginia G. and Kennedy, Richard and Serrano, Geidy E. and Beach, Thomas G. and others},
  title   = {{Distinct subcellular localization of tau and alpha-synuclein in lewy body disease}},
  journal = {Acta Neuropathologica Communications},
  year    = {2025},
  doi     = {10.1186/s40478-024-01913-w},
  pmid    = {39838428},
  url     = {https://doi.org/10.1186/s40478-024-01913-w}
}

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Key findings

The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD.
Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia.
However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD.

Why it matters

This study found that in Lewy body disease, phosphorylated alpha-synuclein rarely colocalized with phosphorylated tau or PAD-tau, though overlap of p-alpha-syn with PAD-tau was associated with LBD. It provides pathological insights but no treatment or cure.

Study details

Evidence strengthLow

How this study scored 39/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Acta Neuropathologica Communications)
Journal's citation record	1 / 4	Acta Neuropathologica Communications: journal h-index 129 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	2 / 7	Cited 7 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	2.3 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 3.9× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	1 / 4	Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Laura A. Volpicelli‐Daley: h-index 45 (OpenAlex, whole career)
Institution's track record	1 / 3	University of Alabama at Birmingham: institution h-index 1,118 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 4 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 39838428)
Free to read	2 / 2	Free to read
Total	39 / 100	—

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