Dataset Information

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age.

ABSTRACT:

Introduction

Tau is a microtubule-associated binding protein implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD). These diseases result in the intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles, the presence of which is associated with cognitive deficits.

Methods

We conducted a longitudinal behavioral study to provide a profile of the TgTau(P301L)23027 transgenic mouse in multiple cognitive domains across multiple ages. P301L is the tau mutation most frequently observed in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and this mouse model recapitulates the progressive development of glial and neurofibrillary tangles, and associated cerebral atrophy observed in patients. We examined frontal cortex-dependent executive function and attention with the touchscreen 5-choice serial reaction time test (5-CSRTT) and assessed the function of temporal cortical structures using novel object recognition (OR).

Results

Despite using sensitive tasks, there were no apparent changes in executive function, attention, or recognition memory in the transgenic mice from 5 to 17 months of age.

Conclusions

This study represents the first comprehensive longitudinal analysis of cognition in the TgTau^P301L mouse model and suggests that this model is not ideal for studying early attention and recognition memory impairments associated with tauopathy. However, spatial and object recognition memory impairments were observed during follow-up assessments when the mice were 18 and 21 months, respectively. These impairments are consistent with previous publications, and with a dementia-like phenotype in these mice when aged.

SUBMITTER: Kent BA

PROVIDER: S-EPMC5853624 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Publications

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age.

Kent Brianne A BA Heath Christopher J CJ Kim Chi Hun CH Ahrens Rosemary R Fraser Paul E PE St George-Hyslop Peter P Bussey Timothy J TJ Saksida Lisa M LM

Brain and behavior 20171218 1

<h4>Introduction</h4>Tau is a microtubule-associated binding protein implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD). These diseases result in the intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles, the presence of which is associated with cognitive deficits.<h4>Methods</h4>We conducted a longitudinal behavioral study to provide a profile of the TgTau(P301L)23027 transgenic mouse in multip ...[more]

PMID: 29568692

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Project description:PurposeTo evaluate visual function (VF) changes in early and intermediate age-related macular degeneration (eAMD and iAMD) over 24 months.DesignProspective, observational natural history study.ParticipantsParticipants were enrolled at the Duke Eye Center.MethodsA total of 101 subjects (33 with eAMD, 47 with iAMD, and 21 normal controls) were recruited. Visual function (VF) tests included best-corrected visual acuity (BCVA), low- luminance visual acuity (LLVA), microperimetry (MP), cone contrast tests (CCTs), and dark adaptation (DA). Mixed-effect model repeated measures based on absolute values and change from baseline identified VF tests differentiating AMD from controls and revealing longitudinal VF decline when controlling for covariates (baseline value, age, coronary artery disease, dry eye, and phakic status). Nine AMD genetic risk variants, combinations of these (genetic burden score), reticular pseudodrusen (RPD), and hyperreflective foci (HRF) were tested as predictors of diagnosis and VF performance.Main outcome measuresLongitudinal changes in VF metrics over 24 months.ResultsA total of 70 subjects completed the 2-year visit (22 with eAMD, 31 with iAMD, and 17 controls). Percent reduced threshold (PRT) on MP and CCT red significantly distinguished iAMD versus controls after 12 and 24 months, respectively. Cone contrast test red, PRT, and absolute threshold (AT) on MP showed significant longitudinal deterioration of VF in iAMD versus baseline at 12 months and onward, however, with a reduced rate of worsening. The DA data confirmed a preexisting functional deficit in iAMD at baseline and revealed an increasing proportion of poorly performing iAMD subjects in DA over the study period. None of the other VF measures showed consistent significant changes among the normal, early, and intermediate groups or over time. The genetic burden score was significantly associated with AMD diagnosis (relative risk for iAMD = 1.64, P < 0.01) and DA (r = 0.42, P = 0.00005). Reticular pseudodrusen and HRF showed moderate associations with DA and weak to moderate associations with MP variables.ConclusionsIn iAMD, MP variables, CCT red, and DA revealed slow and nonlinear functional decline over 24 months. A structure-function relationship in eAMD and iAMD stages was demonstrated among HRF, RPD, and DA, possibly modified by genetic risk factors. These structural and functional features represent potential end points for clinical trials in iAMD.

Dataset Information

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age.

Introduction

Methods

Results

Conclusions

Publications

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age.

Similar Datasets

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