Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
Joseph F Arboleda-VelasquezFrancisco LoperaMichael O'HareSantiago Delgado-TiradoClaudia MarinoNatalia ChmielewskaKahira L Saez-TorresDhanesh AmarnaniAaron P SchultzReisa A SperlingDavid Leyton-CifuentesKewei ChenAna BaenaDavid AguillonSilvia Rios-RomenetsMargarita GiraldoEdmarie Guzmán-VélezDaniel J NortonEnmanuelle Pardilla-DelgadoArabiye ArtolaJustin S SanchezJuliana Acosta-UribeMatthew A LalliKenneth S KosikMatthew J HuentelmanHenrik ZetterbergKaj BlennowRebecca A ReimanJi LuoYinghua ChenPradeep ThiyyaguraYi SuGyungah R JunMarcus NaymikXiaowu GaiMoiz BootwallaJianling JiLishuang ShenJohn B MillerLeo A KimPierre N TariotKeith A JohnsonEric M ReimanYakeel T QuirozPublished in: Nature medicine (2019)
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.