EEG, activity, and sleep architecture in a transgenic AβPPSWE/PSEN1A246E Alzheimer's disease mouse

Amar Jyoti, Andrea Plano, Gernot Riedel, Bettina Platt

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Since sleep and electroencephalogram (EEG) disturbances are endophenotypes of Alzheimer's disease (AD) patients alongside cognitive dysfunction, we here characterized these parameters in transgenic mice carrying transgenes for amyloid-ß protein precursor (AßPPswe) and presenilin 1 (PSEN1A246E) at 5 (pre-plaque) and 20 months, relative to PSEN1 and wild-type (WT) mice, using a novel wireless microchip device. While circadian rhythms were not affected, we obtained significantly higher overall activity at 5 months in the AßPP/PSEN1 strain (p< 0.001) compared to both PSEN1 and WT animals. Vigilance staging revealed that AßPP/PSEN1 animals present with an age-independent increase in wakefulness (p< 0.001) and a decrease in non rapid-eye movement (NREM) sleep (p< 0.01). These changes were age- and genotype-dependent only during the light phase, while dark phase activity pattern were equally affected at both ages. In all genotypes, the amount of REM sleep was lower at 20 months indicating a general age-related profile. Spectral power of qEEG changed in AßPP/PSEN1 mice at 5 months during wakefulness and REM sleep; during wakefulness hippocampal delta (0.5–5 Hz) was reduced and theta (5–9 Hz) power enhanced. By contrast, NREM EEG spectra were affected by age and genotype. Interestingly, PSEN1 animals also showed spectral EEG changes, these differed from both WT and AßPP/PSEN1 animals. Our results indicate that AßPP/PSEN1 mice exhibit abnormalities in activity and sleep architecture preceding amyloid plaque deposition as well as age-related changes in cortical EEG power. Though not fully recapitulating the profile of AD patients, this suggests activity and EEG recordings as sensitive and translational biomarkers in murine models.
Original languageEnglish
Pages (from-to)873-887
Number of pages15
JournalJournal of Alzheimer's Disease
Volume22
Issue number3
DOIs
Publication statusPublished - 21 Sep 2010

Fingerprint

REM Sleep
Electroencephalography
Alzheimer Disease
Sleep
Wakefulness
Genotype
Presenilin-1
Endophenotypes
Wild Animals
Amyloid beta-Protein Precursor
Amyloid Plaques
Circadian Rhythm
Transgenes
Transgenic Mice
Biomarkers
Light
Equipment and Supplies
Power (Psychology)

Keywords

  • EEG Alzheimer wireless

Cite this

EEG, activity, and sleep architecture in a transgenic AβPPSWE/PSEN1A246E Alzheimer's disease mouse. / Jyoti, Amar; Plano, Andrea; Riedel, Gernot; Platt, Bettina.

In: Journal of Alzheimer's Disease, Vol. 22, No. 3, 21.09.2010, p. 873-887.

Research output: Contribution to journalArticle

@article{9d93df0083184c84b7ab3d4c84b9e2ff,
title = "EEG, activity, and sleep architecture in a transgenic AβPPSWE/PSEN1A246E Alzheimer's disease mouse",
abstract = "Since sleep and electroencephalogram (EEG) disturbances are endophenotypes of Alzheimer's disease (AD) patients alongside cognitive dysfunction, we here characterized these parameters in transgenic mice carrying transgenes for amyloid-{\ss} protein precursor (A{\ss}PPswe) and presenilin 1 (PSEN1A246E) at 5 (pre-plaque) and 20 months, relative to PSEN1 and wild-type (WT) mice, using a novel wireless microchip device. While circadian rhythms were not affected, we obtained significantly higher overall activity at 5 months in the A{\ss}PP/PSEN1 strain (p< 0.001) compared to both PSEN1 and WT animals. Vigilance staging revealed that A{\ss}PP/PSEN1 animals present with an age-independent increase in wakefulness (p< 0.001) and a decrease in non rapid-eye movement (NREM) sleep (p< 0.01). These changes were age- and genotype-dependent only during the light phase, while dark phase activity pattern were equally affected at both ages. In all genotypes, the amount of REM sleep was lower at 20 months indicating a general age-related profile. Spectral power of qEEG changed in A{\ss}PP/PSEN1 mice at 5 months during wakefulness and REM sleep; during wakefulness hippocampal delta (0.5–5 Hz) was reduced and theta (5–9 Hz) power enhanced. By contrast, NREM EEG spectra were affected by age and genotype. Interestingly, PSEN1 animals also showed spectral EEG changes, these differed from both WT and A{\ss}PP/PSEN1 animals. Our results indicate that A{\ss}PP/PSEN1 mice exhibit abnormalities in activity and sleep architecture preceding amyloid plaque deposition as well as age-related changes in cortical EEG power. Though not fully recapitulating the profile of AD patients, this suggests activity and EEG recordings as sensitive and translational biomarkers in murine models.",
keywords = "EEG Alzheimer wireless",
author = "Amar Jyoti and Andrea Plano and Gernot Riedel and Bettina Platt",
year = "2010",
month = "9",
day = "21",
doi = "10.3233/JAD-2010-100879",
language = "English",
volume = "22",
pages = "873--887",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "3",

}

TY - JOUR

T1 - EEG, activity, and sleep architecture in a transgenic AβPPSWE/PSEN1A246E Alzheimer's disease mouse

AU - Jyoti, Amar

AU - Plano, Andrea

AU - Riedel, Gernot

AU - Platt, Bettina

PY - 2010/9/21

Y1 - 2010/9/21

N2 - Since sleep and electroencephalogram (EEG) disturbances are endophenotypes of Alzheimer's disease (AD) patients alongside cognitive dysfunction, we here characterized these parameters in transgenic mice carrying transgenes for amyloid-ß protein precursor (AßPPswe) and presenilin 1 (PSEN1A246E) at 5 (pre-plaque) and 20 months, relative to PSEN1 and wild-type (WT) mice, using a novel wireless microchip device. While circadian rhythms were not affected, we obtained significantly higher overall activity at 5 months in the AßPP/PSEN1 strain (p< 0.001) compared to both PSEN1 and WT animals. Vigilance staging revealed that AßPP/PSEN1 animals present with an age-independent increase in wakefulness (p< 0.001) and a decrease in non rapid-eye movement (NREM) sleep (p< 0.01). These changes were age- and genotype-dependent only during the light phase, while dark phase activity pattern were equally affected at both ages. In all genotypes, the amount of REM sleep was lower at 20 months indicating a general age-related profile. Spectral power of qEEG changed in AßPP/PSEN1 mice at 5 months during wakefulness and REM sleep; during wakefulness hippocampal delta (0.5–5 Hz) was reduced and theta (5–9 Hz) power enhanced. By contrast, NREM EEG spectra were affected by age and genotype. Interestingly, PSEN1 animals also showed spectral EEG changes, these differed from both WT and AßPP/PSEN1 animals. Our results indicate that AßPP/PSEN1 mice exhibit abnormalities in activity and sleep architecture preceding amyloid plaque deposition as well as age-related changes in cortical EEG power. Though not fully recapitulating the profile of AD patients, this suggests activity and EEG recordings as sensitive and translational biomarkers in murine models.

AB - Since sleep and electroencephalogram (EEG) disturbances are endophenotypes of Alzheimer's disease (AD) patients alongside cognitive dysfunction, we here characterized these parameters in transgenic mice carrying transgenes for amyloid-ß protein precursor (AßPPswe) and presenilin 1 (PSEN1A246E) at 5 (pre-plaque) and 20 months, relative to PSEN1 and wild-type (WT) mice, using a novel wireless microchip device. While circadian rhythms were not affected, we obtained significantly higher overall activity at 5 months in the AßPP/PSEN1 strain (p< 0.001) compared to both PSEN1 and WT animals. Vigilance staging revealed that AßPP/PSEN1 animals present with an age-independent increase in wakefulness (p< 0.001) and a decrease in non rapid-eye movement (NREM) sleep (p< 0.01). These changes were age- and genotype-dependent only during the light phase, while dark phase activity pattern were equally affected at both ages. In all genotypes, the amount of REM sleep was lower at 20 months indicating a general age-related profile. Spectral power of qEEG changed in AßPP/PSEN1 mice at 5 months during wakefulness and REM sleep; during wakefulness hippocampal delta (0.5–5 Hz) was reduced and theta (5–9 Hz) power enhanced. By contrast, NREM EEG spectra were affected by age and genotype. Interestingly, PSEN1 animals also showed spectral EEG changes, these differed from both WT and AßPP/PSEN1 animals. Our results indicate that AßPP/PSEN1 mice exhibit abnormalities in activity and sleep architecture preceding amyloid plaque deposition as well as age-related changes in cortical EEG power. Though not fully recapitulating the profile of AD patients, this suggests activity and EEG recordings as sensitive and translational biomarkers in murine models.

KW - EEG Alzheimer wireless

U2 - 10.3233/JAD-2010-100879

DO - 10.3233/JAD-2010-100879

M3 - Article

C2 - 20858963

VL - 22

SP - 873

EP - 887

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 3

ER -