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50/100

✓ Peer-reviewed alzhub usefulness score 50 out of 100. Down syndrome and Alzheimer's

Topic: Brain proteins, microglia and lab models

Beta-secretase (BACE1) is the rate-limiting protease for the generation of the amyloid beta-peptide (Abeta) in Alzheimer disease. Mice in which the bace1 gene is inactivated are reported to be healthy. However, the presence of a homologous gene encoding BACE2 raises the possibility of compensatory mechanisms. Therefore, we have generated bace1, bace2, and double knockout mice. We report here that BACE1 mice display a complex phenotype. A variable but significant number of BACE1 offspring died in the first weeks after birth. The surviving mice remained smaller than their littermate controls and presented a hyperactive behavior. Electrophysiologically, subtle alterations in the steady-state inactivation of voltage-gated sodium channels in BACE1-deficient neurons were observed. In contrast, bace2 knockout mice displayed an overall healthy phenotype. However, a combined deficiency of BACE2 and BACE1 enhanced the bace1-/- lethality phenotype. At the biochemical level, we have confirmed that BACE1 deficiency results in an almost complete block of Abeta generation in neurons, but not in glia. As glia are 10 times more abundant in brain compared with neurons, our data indicate that BACE2 could indeed contribute to Abeta generation in the brains of Alzheimer disease and, in particular, Down syndrome patients. In conclusion, our data challenge the general idea of BACE1 as a safe drug target and call for some caution when claiming that no major side effects should be expected from blocking BACE1 activity.

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

APA 7th

Dominguez, D., Tournoy, J., Hartmann, D., Huth, T., Cryns, K., Deforce, S., et al. (2005). Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m505249200

Vancouver

Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, et al. Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m505249200. PMID: 15987683.

BibTeX

@article{dominguez2005-15987683,
  author  = {Dominguez, D. and Tournoy, J. and Hartmann, D. and Huth, T. and Cryns, K. and Deforce, S. and Serneels, L. and Camacho, I. E. and others},
  title   = {{Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice}},
  journal = {The Journal of biological chemistry},
  year    = {2005},
  doi     = {10.1074/jbc.m505249200},
  pmid    = {15987683},
  url     = {https://doi.org/10.1074/jbc.m505249200}
}

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Key findings

A variable but significant number of BACE1 offspring died in the first weeks after birth.
In contrast, bace2 knockout mice displayed an overall healthy phenotype.
At the biochemical level, we have confirmed that BACE1 deficiency results in an almost complete block of Abeta generation in neurons, but not in glia.
As glia are 10 times more abundant in brain compared with neurons, our data indicate that BACE2 could indeed contribute to Abeta generation in the brains of Alzheimer disease and, in particular, Down syndrome patients.
In conclusion, our data challenge the general idea of BACE1 as a safe drug target and call for some caution when claiming that no major side effects should be expected from blocking BACE1 activity.

Why it matters

In mice, removing the BACE1 gene almost completely blocked amyloid beta production in neurons but caused health problems and early death, while BACE2 removal appeared harmless. The findings suggest that BACE2 may also contribute to amyloid beta production in the brain, which raises questions about the safety of targeting BACE1 as a treatment.

Study details

Evidence strengthLow

How this study scored 50/100

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

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The Journal of biological chemistry)
Journal's citation record	4 / 4	Journal of Biological Chemistry: journal h-index 780 (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	2005 — older than 20 years, still counted
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	Laboratory or animal study (title names “mice”) — scores zero
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	6 / 7	Cited 361 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	15.7 citations a year over 23 year(s) since 2005
Impact for its field and year	4 / 6	Cited 10.2× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 19 other studies in this library
Still being cited	2 / 4	Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Bart De Strooper: h-index 146 (OpenAlex, whole career)
Institution's track record	1 / 3	KU Leuven: institution h-index 1,386 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 5 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 15987683)
Free to read	0 / 2	Behind a paywall — scores zero
Total	50 / 100	—

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