@article {1647870,
	title = {Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer{\textquoteright}s dementia},
	journal = {Acta Neuropathol},
	volume = {144},
	number = {3},
	year = {2022},
	month = {2022 09},
	pages = {589-601},
	abstract = {We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer{\textquoteright}s disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer{\textquoteright}s symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may\&nbsp;impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.},
	keywords = {Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E3, Brain, Homozygote, Humans, Positron-Emission Tomography, tau Proteins},
	issn = {1432-0533},
	doi = {10.1007/s00401-022-02467-8},
	author = {Sepulveda-Falla, Diego and Sanchez, Justin S and Almeida, Maria Camila and Boassa, Daniela and Acosta-Uribe, Juliana and Vila-Castelar, Clara and Ramirez-Gomez, Liliana and Baena, Ana and Aguillon, David and Villalba-Moreno, Nelson David and Littau, Jessica Lisa and Villegas, Andres and Beach, Thomas G and White, Charles L and Mark Ellisman and Krasemann, Susanne and Glatzel, Markus and Johnson, Keith A and Sperling, Reisa A and Reiman, Eric M and Arboleda-Velasquez, Joseph F and Kosik, Kenneth S and Lopera, Francisco and Quiroz, Yakeel T}
}
