The role of clusterin, complement receptor 1, and phosphatidylinositol binding clathrin assembly protein in Alzheimer disease risk and cerebrospinal fluid biomarker levels
Schjeide BM, Schnack C, Lambert JC, Lill CM, Kirchheiner J, Tumani H, Otto M, Tanzi RE et al.. Archives of general psychiatry, 2011-02-01
Topic: Brain proteins, microglia and lab models
Context Two recent and simultaneously published genome-wide association studies independently implicated clusterin (CLU), complement receptor 1 (CR1), and phosphatidylinositol binding clathrin assembly protein (PICALM) as putative novel Alzheimer disease (AD) risk loci. Despite their strong statistical support, all 3 signals emerged from heterogeneous case-control populations and lack replication in different settings. Objective To determine whether genetic variants in CLU, CR1, and PICALM confer risk for AD in independent data sets (n = 4254) and to test the impact of these markers on cerebrospinal fluid (CSF)-Aβ42 and total-tau protein levels (n = 425). Design Genetic association study using family-based and case-control designs. Setting Ambulatory or hospitalized care. Participants Family samples originate from mostly multiplex pedigrees recruited at different centers in the United States (1245 families, 2654 individuals with AD, and 1175 unaffected relatives). Unrelated case-control subjects originate from 1 clinical center in Germany (214 individuals with AD and 211 controls). All subjects were of European descent. Main outcome measures The association between 5 genetic variants in CLU, CR1, and PICALM and risk for AD, and the correlation between these 5 genetic variants and CSF-Aβ42 and tau levels. Results All 3 investigated loci showed significant associations between risk for AD (1-tailed P values ranging from Conclusions This study provides compelling independent evidence that genetic variants in CLU, CR1, and PICALM are genetically associated with risk for AD. Furthermore, the CSF biomarker analyses provide a first insight into the potentially predominant pathogenetic mechanism(s) underlying the association between AD risk and PICALM.
Key findings
- Results All 3 investigated loci showed significant associations between risk for AD (1-tailed P values ranging from Conclusions This study provides compelling independent evidence that genetic variants in CLU, CR1, and PICALM are genetically associated with risk for AD.
Why it matters
Two earlier genome-wide studies flagged the genes CLU, CR1 and PICALM as possible Alzheimer risk genes, but the signals had not been confirmed in other settings. This study tested 5 variants in 4,254 people of European descent — US families with several affected members and a German case-control group — and found that all three genes were significantly associated with Alzheimer risk. The authors call this "compelling independent evidence" of a genetic link; it shows an association with risk, not a cause, a test or a treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcase-control study
- Participants4,254
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of general psychiatry) |
| Journal's citation record | 4 / 4 | Archives of General Psychiatry: journal h-index 543 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 4,254 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.8 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 1 / 4 | Cited 10 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lars Bertram: h-index 77 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Max Planck Society: institution h-index 1,183 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21300948) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Schjeide, B. M., Schnack, C., Lambert, J. C., Lill, C. M., Kirchheiner, J., Tumani, H., et al. (2011). The role of clusterin, complement receptor 1, and phosphatidylinositol binding clathrin assembly protein in Alzheimer disease risk and cerebrospinal fluid biomarker levels. Archives of general psychiatry. https://doi.org/10.1001/archgenpsychiatry.2010.196
Vancouver
Schjeide BM, Schnack C, Lambert JC, Lill CM, Kirchheiner J, Tumani H, et al. The role of clusterin, complement receptor 1, and phosphatidylinositol binding clathrin assembly protein in Alzheimer disease risk and cerebrospinal fluid biomarker levels. Archives of general psychiatry. 2011. doi:10.1001/archgenpsychiatry.2010.196. PMID: 21300948.
BibTeX
@article{schjeide2011-21300948,
author = {Schjeide, B. M. and Schnack, C. and Lambert, J. C. and Lill, C. M. and Kirchheiner, J. and Tumani, H. and Otto, M. and Tanzi, R. E. and others},
title = {{The role of clusterin, complement receptor 1, and phosphatidylinositol binding clathrin assembly protein in Alzheimer disease risk and cerebrospinal fluid biomarker levels}},
journal = {Archives of general psychiatry},
year = {2011},
doi = {10.1001/archgenpsychiatry.2010.196},
pmid = {21300948},
url = {https://doi.org/10.1001/archgenpsychiatry.2010.196}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
8 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.