Alzheimer's disease alters astrocytic functions related to neuronal support andtranscellular internalization of mitochondria

Riikka Lampinen; Irina Belaya; Liudmila Saveleva; Jeffrey R. Liddell; Dzhessi Rait; Mikko T. Huuskonen; Raisa Giniatullina; Annika Sorvari; Liisi Soppela; Nikita Mikhailov; Isabella Boccuni; Rashid A. Giniatullin; Marcela Cruz-Haces; Julia Konovalova; Marja Koskuvi; Tuomas H. Rauramaa; Andrii Domanskyi; Riikka H. Hämäläinen; Gundars Goldsteins; Jari Koıstınaho; Tarja Malm; Sweelin Chew; Kirsi J. Rilla; Anthony Robert White; Nicholas Marsh‐Armstrong; Katja M. Kanninen

doi:10.1101/2021.09.15.460570

NeurosciencebioRxivSep 15, 2021

Preprint

Alzheimer's disease alters astrocytic functions related to neuronal support andtranscellular internalization of mitochondria

Riikka Lampinen iD, Irina Belaya iD, Liudmila Saveleva iD, Jeffrey R. Liddell iD, Dzhessi Rait, Mikko T. Huuskonen iD, Raisa Giniatullina, Annika Sorvari iD, Liisi Soppela, Nikita Mikhailov iD, Isabella Boccuni iD, Rashid A. Giniatullin iD, Marcela Cruz-Haces iD, Julia Konovalova iD, Marja Koskuvi iD, Tuomas H. Rauramaa iD, Andrii Domanskyi iD, Riikka H. Hämäläinen iD, Gundars Goldsteins, Jari Koıstınaho iD, Tarja Malm iD, Sweelin Chew iD, Kirsi J. Rilla iD, Anthony Robert White iD, Nicholas Marsh‐Armstrong iD, Katja M. Kanninen iD

Abstract

Under physiological conditions in vivo astrocytes internalize and degrade neuronal mitochondria in a process called transmitophagy. Mitophagy is widely reported to be impaired in neurodegeneration but it is unknown whether and how transmitophagy is altered in Alzheimers disease (AD). Here we report that the internalization and degradation of neuronal mitochondria are significantly increased in astrocytes isolated from aged AD mouse brains. We also demonstrate for the first time a similar phenomenon between human neurons and AD astrocytes, and in murine hippocampi in vivo. The results suggest the involvement of S100a4 in impaired mitochondrial transfer between neurons and aged AD astrocytes. Significant increases in the mitophagy regulator Ambra1 were observed in the aged AD astrocytes. These findings demonstrate altered neuron-supporting functions of aged AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.

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