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000257575 1001_ $$00000-0002-5874-944X$$aKommaddi, Reddy Peera$$b0
000257575 245__ $$aSex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort.
000257575 260__ $$aLondon$$bNature Publishing Group$$c2023
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000257575 520__ $$aWomen carry a higher burden of Alzheimer's disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and in APPswe/PS1ΔE9 mice. Activity dependent protein translation and associative learning and memory deficits were examined in APPswe/PS1ΔE9 mice and wild-type mice. As a human comparator group, progression of cognitive dysfunction was assessed in mutation carriers and non-carriers from DIAN (Dominantly Inherited Alzheimer Network) cohort. Female APPswe/PS1ΔE9 mice did not show recall deficits after contextual fear conditioning until 8 months of age. Further, activity dependent protein translation and Akt1-mTOR signaling at the synapse were impaired in male but not in female mice until 8 months of age. Ovariectomized APPswe/PS1ΔE9 mice displayed recall deficits at 4 months of age and these were sustained until 8 months of age. Moreover, activity dependent protein translation was also impaired in 4 months old ovariectomized APPswe/PS1ΔE9 mice compared with sham female APPswe/PS1ΔE9 mice. Progression of memory impairment differed between men and women in the DIAN cohort as analyzed using linear mixed effects model, wherein men showed steeper cognitive decline irrespective of the age of entry in the study, while women showed significantly greater performance and slower decline in immediate recall (LOGIMEM) and delayed recall (MEMUNITS) than men. However, when the performance of men and women in several cognitive tasks (such as Wechsler's logical memory) are compared with the estimated year from expected symptom onset (EYO) we found no significant differences between men and women. We conclude that in familial AD patients and mouse models, females are protected, and the onset of disease is delayed as long as estrogen levels are intact.
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000257575 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000257575 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000257575 650_2 $$2MeSH$$aHumans
000257575 650_2 $$2MeSH$$aFemale
000257575 650_2 $$2MeSH$$aMale
000257575 650_2 $$2MeSH$$aMice
000257575 650_2 $$2MeSH$$aAnimals
000257575 650_2 $$2MeSH$$aInfant
000257575 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000257575 650_2 $$2MeSH$$aMice, Transgenic
000257575 650_2 $$2MeSH$$aSex Characteristics
000257575 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000257575 650_2 $$2MeSH$$aFear
000257575 650_2 $$2MeSH$$aMemory Disorders
000257575 650_2 $$2MeSH$$aDisease Models, Animal
000257575 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000257575 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000257575 693__ $$0EXP:(DE-2719)DIAN-20090101$$5EXP:(DE-2719)DIAN-20090101$$eLongitudinal Study on Dominantly Inherited Alzheimer's Disease$$x0
000257575 7001_ $$aVerma, Aditi$$b1
000257575 7001_ $$aMuniz-Terrera, Graciela$$b2
000257575 7001_ $$aTiwari, Vivek$$b3
000257575 7001_ $$aChithanathan, Keerthana$$b4
000257575 7001_ $$aDiwakar, Latha$$b5
000257575 7001_ $$aGowaikar, Ruturaj$$b6
000257575 7001_ $$aKarunakaran, Smitha$$b7
000257575 7001_ $$aMalo, Palash Kumar$$b8
000257575 7001_ $$aGraff-Radford, Neill R$$b9
000257575 7001_ $$00000-0001-5133-5538$$aDay, Gregory S$$b10
000257575 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b11$$udzne
000257575 7001_ $$0P:(DE-2719)2811820$$aVöglein, Jonathan$$b12$$udzne
000257575 7001_ $$0P:(DE-2719)9001761$$aNübling, Georg$$b13$$udzne
000257575 7001_ $$00000-0001-8828-8085$$aIkeuchi, Takeshi$$b14
000257575 7001_ $$00000-0002-2178-0769$$aKasuga, Kensaku$$b15
000257575 7001_ $$aNetwork, Dominantly Inherited Alzheimer$$b16$$eCollaboration Author
000257575 7001_ $$00000-0003-3226-0782$$aRavindranath, Vijayalakshmi$$b17
000257575 773__ $$0PERI:(DE-600)2609311-X$$a10.1038/s41398-023-02411-8$$gVol. 13, no. 1, p. 123$$n1$$p123$$tTranslational Psychiatry$$v13$$x2158-3188$$y2023
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