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Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members
Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, Bisceglio G, Rovelet-Lecrux A et al.. Brain : a journal of neurology, 2009-01-21
Topic: Brain proteins, microglia and lab models
Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. The clinical presentation associated with GRN mutations is heterogeneous and may include clinical probable Alzheimer's disease. All GRN mutations identified thus far cause disease through a uniform disease mechanism, i.e. the loss of functional GRN or haploinsufficiency. To determine if expression of GRN in plasma could predict GRN mutation status and could be used as a biological marker, we optimized a GRN ELISA and studied plasma samples of a consecutive clinical FTLD series of 219 patients, 70 control individuals, 72 early-onset probable Alzheimer's disease patients and nine symptomatic and 18 asymptomatic relatives of GRN mutation families. All FTLD patients with GRN loss-of-function mutations showed significantly reduced levels of GRN in plasma to about one third of the levels observed in non-GRN carriers and control individuals (P < 0.001). No overlap in distributions of GRN levels was observed between the eight GRN loss-of-function mutation carriers (range: 53-94 ng/ml) and 191 non-GRN mutation carriers (range: 115-386 ng/ml). Similar low levels of GRN were identified in asymptomatic GRN mutation carriers. Importantly, ELISA analyses also identified one probable Alzheimer's disease patient (1.4%) carrying a loss-of-function mutation in GRN. Biochemical analyses further showed that the GRN ELISA only detects full-length GRN, no intermediate granulin fragments. This study demonstrates that using a GRN ELISA in plasma, pathogenic GRN mutations can be accurately detected in symptomatic and asymptomatic carriers. The approximately 75% reduction in full-length GRN, suggests an unbalanced GRN metabolism in loss-of-function mutation carriers whereby more GRN is processed into granulins. We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals.
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APA 7th
Finch, N., Baker, M., Crook, R., Swanson, K., Kuntz, K., Surtees, R., et al. (2009). Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain : a journal of neurology. https://doi.org/10.1093/brain/awn352
Vancouver
Finch N, Baker M, Crook R, Swanson K, Kuntz K, Surtees R, et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain : a journal of neurology. 2009. doi:10.1093/brain/awn352. PMID: 19158106.
BibTeX
@article{finch2009-19158106,
author = {Finch, N. and Baker, M. and Crook, R. and Swanson, K. and Kuntz, K. and Surtees, R. and Bisceglio, G. and Rovelet-Lecrux, A. and others},
title = {{Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members}},
journal = {Brain : a journal of neurology},
year = {2009},
doi = {10.1093/brain/awn352},
pmid = {19158106},
url = {https://doi.org/10.1093/brain/awn352}
}
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Key findings
- The clinical presentation associated with GRN mutations is heterogeneous and may include clinical probable Alzheimer's disease.
- All FTLD patients with GRN loss-of-function mutations showed significantly reduced levels of GRN in plasma to about one third of the levels observed in non-GRN carriers and control individuals (P < 0.001).
- Biochemical analyses further showed that the GRN ELISA only detects full-length GRN, no intermediate granulin fragments.
Why it matters
Low levels of progranulin in plasma were found in people with progranulin mutations, including some without symptoms, and one person with probable Alzheimer's disease was identified. This is a biomarker finding only and does not show any treatment, cure or prevention for Alzheimer's disease.
Study details
- Participants219
- Effect size1.4%
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 1 / 5 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 219 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 6 / 7 | Cited 386 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.3 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 18.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 2 / 4 | Cited 42 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Roos Rademakers: h-index 5 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19158106) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
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