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Using anxiety as a sex‐specific neuropsychiatric biomarker of Alzheimer’s disease
Author(s) -
Hunsberger Holly C.,
Lee Seonjoo,
Cha Jiook,
Denny Christine Ann
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037201
Subject(s) - anxiety , depression (economics) , neurodegeneration , disease , biomarker , psychology , population , atrophy , neuroscience , memory impairment , medicine , psychiatry , cognition , biology , biochemistry , environmental health , economics , macroeconomics
Background Neuropsychiatric disturbances, such as depression and anxiety, are observed in 90% of Alzheimer’s disease (AD) patients and are frequent in those at risk for AD. However, until recently, much of the research narrowly targeted co‐morbid depression. Clinical reports have provided evidence that anxiety symptoms predict the conversion to AD, over and beyond the effects of depression, memory loss, and even atrophy. Similarly, epidemiological studies show that neurodegeneration and clinical symptoms occur more rapidly in females once diagnosed. Although most AD studies have been performed using male mice, females represent two‐thirds of the AD population and are more susceptible to depression and anxiety. Method To study how anatomical sex and anxiety impact AD progression, I used our activity‐dependent tagging system mice. These mice allow for brain‐wide indelible labeling of neurons activated during learning, which then can be compared with secondary neuronal ensembles activated during memory retrieval. The neurons activated at both time points represent a memory trace or engram. Here, we aimed to identify the neural ensembles linking anxiety and memory loss following AD progression by utilizing behavioral studies, calcium imaging and whole‐brain microscopy, in female and male mice. Result We found: 1) Female AD mice exhibited anxiety‐like behavior at an earlier age compared to controls and male mice, 2) AD female mice displayed memory deficits as early as 2 months of age, 3) Anxiety‐like behavior correlated with memory impairment only in AD female mice, and 4) Unlike their male counterparts, female AD mice showed a decline in memory traces in the CA3 of the hippocampus. Conclusion We now believe that anxiety could represent a neuropsychiatric predictor of AD and are currently working to translate these findings to humans using the Alzheimer’s disease neuroimaging initiative (ADNI) dataset. We have found that in humans, anxiety predicts transition to dementia and that anxiety has a sex‐specific effect on brain atrophy.