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Table 1 Sex Differences in cognition and behavior in mouse models of AD

From: Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

  Hormone Status, Age Comparison Cognition & Behavioral Measure and Ref. AD Tg Model
Baseline Intact, 8 mos (F), 12 mos (M) Intact: F vs M F Tg ↑ activity vs F Ntg; M Tg no deficit (OF) [114] APPswe-PS1dE9
Intact, 2–15 mos [115], 6–10 mos [121] Intact: F vs M F Tg ↓spatial/fear memory at some ages vs F Ntg & M Tg (MWM, PA) [115] 3xTg-AD [115]
F Tg↔M Tg impairment in novel object recognition (NOR) [115, 121] TASTPM [121]
Intact, 2–14 mos Intact: F vs M F Tg ↓ SAB at 12-14 mos vs F Ntg and M Tg (Y-maze) [116] 3xTg-AD
Intact, 2–17 mos Intact: F vs M F Tg impaired and no change with age (CTA) [127] APPswe/ PS1dE9
M Tg increasingly impaired with age (CTA) [127]
Intact, 6 mos Intact: F vs M F Tg ↓activity/spatial memory/novel arm preference vs F Ntg; M Tg no deficit (OF, MWM, Y-maze) [117] 3xTg-AD
Intact, 6 mos Intact: F vs M F Tg ↑ activity & ↑entries into light vs F Ntg; M Tg vice versa (OF, DLB) [118] 3xTg-AD
  Intact, 3, 9 mos Intact: F vs M M Tg ↑activity & ↓SAB vs M Ntg; F Tg no deficit (OF, Y-maze) [119] APPsw
F Tg ↓spatial memory vs F Ntg 3 mos; M Tg no deficit (Circular Platform)A, [119]
Intact,16 mos Intact: F vs M F Tg↔M Tg impairment in spatial acquisition memory (Barnes Maze) [122] APPswe/ PS1dE9
Intact, 3, 9 mos [119], 6 mos [118] Intact: F vs M F↔M, Tg↔Ntg, no spatial learning impairments (MWM) [118, 119] APPsw [119]
3xTg-AD [118]
  Intact, 6, 15 mos Intact: F vs M M Tg ↑center time vs F Tg and M Ntg (OF) [120] 3xTg-AD
Response to Manipulation Intact, 8 mos (F), 12 mos (M) Intact: F vs M COX-2 overexp ↓SAB in F Tg; no change or impairment in M Tg (Y-maze) [114] APPswe/ PS1dE9
COX-2 overexp ↔ novel arm preferenceB in F or M, Tg or Ntg (Y-maze) [114]
Intact, 6 mos Intact: F vs M Running ↑open arm entries in F Tg & Ntg and ↓ in M Tg & Ntg (EPMC) [117] 3xTg-AD
  Intact, 6 mos Intact: F vs M Running ↑spatial memory/novel arm preference in F Tg vs non-running F Tg; no effect or impairment in M Tg (MWM, Y-maze) [117] 3xTg-AD
  1. Symbols: ↑=increase, ↓=decrease, ↔=no change or difference.
  2. Abbreviations: F=Female, M=Male, Ntg=non-transgenic, Tg=transgenic, mos=months, d=day, SAB=spontaneous alternating behavior (thought to reflect working memory), MWM=Morris water maze, OF=open field, PA=passive avoidance, CTA=conditioned taste aversion, NOR=novel object recognition, DLB=dark-light box, EPM=elevated plus maze, COX-2=cyclooxygenase 2, overexp=overexpression.
  3. A, Latency to reach escape hole and number of errors.
  4. B, Preference for the novel arm in Y-maze thought to reflect spatial recognition memory [114].
  5. C, No 3xTg-AD effect was observed in the EPM [117].