Per Nilsson (Sweden)
Karolinska Instituet
Department of Neurobiology, Care Sciences and Society (NVS) Division of Clinical Geriatrics
I am working on finding the molecular underpinnings of Alzheimer’s disease. My background is a PhD in molecular biotechnology from Uppsala University, Sweden. I did my postdoc at RIKEN Brain Science Institute, Japan. Since 2016 I am heading a research group at Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Sweden, where I am also vice/acting head of Division of Neurogeriatrics. Our research is focused on preclinical studies using animal models of Alzheimer’s in combination with clinical studies. The research is very much focused on protein homeostasis and the role of autophagy in amyloid β and tau metabolism, the two hallmarks of Alzheimer’s disease. This has led to pivotal findings showing that autophagy mediates the secretion of Alzheimer-causing amyloid β and that impaired autophagy during Alzheimer progression leads to neurodegeneration.

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 Conference Calendar

INCREASED UCB-J PET AND EXCITATORY POSTSYNAPTIC POTENTIAL CORRELATES WITH RELEASE OF CSF NEUROGRANIN AND TAU IN APP KNOCK-IN MICE

Session Name
0770 - AD: DISEASE MECHANISMS, PATHOPHYSIOLOGY: SYNAPTIC INTEGRITY & PLASTICITY (ID 135)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:30 PM
Room
ONSITE: 131-132
Lecture Time
03:15 PM - 03:30 PM
Presenter

Abstract

Aims

To investigate the translational potential of CSF Ng for synaptic alterations using the App knock-in AD mice.

Methods

CSF and brain tissue were sampled from 12-months old wild type (WT), AppNL-F/NL-F and AppNL-G-F/NL-G-F mice. Ng, Aβ42, and t-tau levels were analyzed using Simoa. UCB-J PET was performed using [18F]SynVesT-1 and nanoPET. Amplitude and frequency of miniature EPSCs were measured by patch clamp recordings of cornu ammonis 1 exitatory neurons.

Results

Ng and tau levels were significantly increased in CSF of App knock-in mice, most pronounced in AppNL-G-F mice. CSF Ng levels negatively correlated with Ng levels in the cortex and Aβ42 levels in the CSF and positively correlated with tau levels both in the CSF and brain tissue. IHC staining revealed a substantial reduction of Ng around Aβ plaques. Frequency of the miniature EPSCs and UCB-J PET signal is similarly increased in AppNL-G-F mice.

Conclusions

App knock-in mice exhibit Aβ, tau and Ng alterations in the CSF and the interdependencies between these pathologies were strikingly similar to the pattern previously observed in AD patients. The changes in the mouse CSF biomarker readout were concurrent with synaptic impairments shown by increased UCB-J PET signal and hyperexcitability as shown by increased synaptic firing frequency. Hence, App knock-in mice and their CSF biomarkers have translational value for investigating synaptic alterations due to AD-related pathologies.

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