Mitochondrial dysfunction and immune activation are detectable in early alzheimer's disease blood

Katie Lunnon, Zina Ibrahima, Petroula Proitsi, Anbarasu Lourdusamy, Stephen Newhouse, Martina Sattlecker, Simon Furney, Muzamil Saleem, Hilkka Soininen, Iwona Kłoszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Giovanni Coppola, Daniel Geschwind, Andrew Simmons, Simon Lovestone, Richard Dobson, Angela Hodges

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Alzheimer's disease (AD), like other dementias, is characterized by progressive neuronal loss and neuroinflammation in the brain. The peripheral leukocyte response occurring alongside these brain changes has not been extensively studied, but might inform therapeutic approaches and provide relevant disease biomarkers. Using microarrays, we assessed blood gene expression alterations occurring in people with AD and those with mild cognitive changes at increased risk of developing AD. Of the 2,908 differentially expressed probes identified between the three groups (p < 0.01), a quarter were altered in blood from mild cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a peripheral response to pathology may occur very early. There was strong evidence for mitochondrial dysfunction with decreased expression of many of the respiratory complex I-V genes and subunits of the core mitochondrial ribosome complex. This mirrors changes previously observed in AD brain. A number of genes encoding cell adhesion molecules were increased, along with other immune-related genes. These changes are consistent with leukocyte activation and their increased the transition from circulation into the brain. In addition to expression changes, we also found increased numbers of basophils in people with MCI and AD, and increased monocytes in people with an AD diagnosis. Taken together this study provides both an insight into the functional response of circulating leukocytes during neurodegeneration and also identifies potential targets such as the respiratory chain for designing and monitoring future therapeutic interventions using blood.

Original languageEnglish
Pages (from-to)685-710
Number of pages26
JournalJournal of Alzheimer's Disease
Volume30
Issue number3
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Alzheimer's disease
  • blood
  • gene expression pattern analysis
  • inflammation
  • late onset
  • mild cognitive impairment
  • mitochondria

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