Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta

By A. Griciuc, A. Serrano‐Pozo, A. Parrado, Andrea N. Lesinski, Caroline Asselin, K. Mullin, B. Hooli, Se Hoon Choi, Bradley T. Hyman, Rudolph E. Tanzi. Neuron, 2013

917 citations recorded by the source corpus.

SUMMARY The transmembrane protein CD33 is a sialic acid-binding immunoglobulin-like lectin that regulates innate immunity but has no known functions in the brain. We have previously shown that the CD33 gene is a risk factor for Alzheimer’s disease (AD). Here, we observed increased expression of CD33 in microglial cells in AD brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (Aβ42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble Aβ42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of Aβ42 in microglial cell cultures. Finally, brain levels of insoluble Aβ42 as well as amyloid plaque burden were markedly reduced in APPSwe/PS1ΔE9/CD33−/− mice. Therefore, CD33 inactivation mitigates Aβ pathology and CD33 inhibition could represent a novel therapy for AD.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/fc913c815aa6d481c8d371f7c668e65f63cde4a9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Long
2. A. Goate
3. Bradley T. Hyman
4. Joachim L. Schultze
5. D. Holtzman
6. B. de Strooper

In Neurology

1. D. Holtzman
2. J. Long
3. A. Goate
4. V. Perry
5. Joachim L. Schultze
6. C. Cunningham
7. R. Ransohoff

In Physiology

1. J. Long
2. D. Holtzman
3. A. Goate
4. E. Karran
5. B. de Strooper
6. Bradley T. Hyman
7. V. Perry
8. T. Saido

Citations in the corpus

• Alzheimer's disease risk genes and mechanisms of disease pathogenesis (2014, positive): “The minor allele of rs3865444 is associated with reduced CD33 mRNA expression and insoluble Aβ42 in brains with AD (88).”
• Microglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response (2018, background): “Increased levels of this receptor have been correlated with an elevated risk of AD due to slower microglial phagocytosis and Aβ clearance, leading to an increased in plaque deposition in AD mice brains (Griciuc et al., 2013; Jiang et al., 2014).”
• Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “Thus, factors such as CD33, which impedes Aβ phagocytosis by microglia, has been considered to increase the risk for suffering from AD.(169) However, the prolonged activation of microglia become enlarged and are no longer able to exert their phagocytic function.”