[Abstract Title]. - Society for Neuroscience

Authors: *K. KIPIANI, T. A. MILNER, G. K. GOURAS, F. M. BEAL, M. T. LIN;
Neurol. & Neurosci., Weill Med. Col. Cornell Univ., New York, NY
Abstract: Intracellular accumulation of amyloid-β peptide (Aβ) is increasingly recognized as a
contributor to the Alzheimer‟s disease (AD) pathogenesis. Mitochondrial impairment is also
implicated in the AD pathogenesis. To investigate whether mitochondria are a site of
intracellular Aβ accumulation, we performed subcellular fractionation and immunoelectron
microscopy studies on brains of Tg19959 mice, which express a doubly mutant human amyloid
precursor protein (APP) and are characterized by accelerated production and deposition of Aβ42.
We found that Aβ is present in mitochondrially enriched fractions, and is resistant to the
treatment with nonionic detergent and to the proteolytic digestion, suggesting its localization to a
membrane protected compartment of mitochondrial origin. Synthetic Aβ gets also incorporated
within the same membrane-protected compartment. By immunoelectron microscopy, we found
that some but not all mitochondria in Tg19959 mouse brains were immunoreactive for Aβ or
APP C-terminal fragments (APP CTFs). We found this in both very young mice and after plaque
deposition. In the hippocampus, mitochondria with Aβ immunoreactivity were most common in
distal neuronal processes in layers containing synaptic fields. Mitochondria immunoreactive for
APP CTFs occurred in both neuronal and astroglial processes. The astroglial processes
containing APP CTF-immunoreactive mitochondria were typically heavily labeled by APP CTFs
and were morphologically altered. Because mitochondria are important in synaptic function,
mitochondrial Aβ and APP CTFs within neuronal and glial processes could contribute to
synaptic dysfunction in AD.
Disclosures: K. Kipiani , None; T.A. Milner, None; G.K. Gouras, None; F.M. Beal,
None; M.T. Lin, None.
Poster