Alzheimer's disease pathophysiology in the Retina

Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status

“…These tau forms are primarily found within neurons in the INL and GCL. Inconsistencies in previous observations likely stem from variations in the geometric regions that were analyzed, as well as tissue preservation, fixation, and staining protocols [ 3 , 27 ].…”

“…However, this is speculative for the current study and merits future quantitative investigation of the spatiotemporal distribution of tau isoforms in different retinal quadrants and layers during disease stages to confirm these observations. In addition, given the inconsistencies in previous reports on retinal AD tauopathy—where several studies identified certain pathological tau forms in the AD retina [ 21 , 31 , 34 , 65 , 87 ] that two earlier reports could not detect [ 36 , 88 ] or could partially detect [ 20 , 70 ]—workshop groups focused on harmonizing the methodologies for analyzing retinal tauopathy will be useful in future research [ 27 ].…”

“…The retina, an extension of the brain and the only central nervous system (CNS) organ not shielded by bone [ 24 , 66 ], holds promise for revolutionizing AD screening. Current limitations in early diagnosis and monitoring of AD in the clinical settings [ 3 , 41 ], make retinal imaging a potential solution due to its accessibility for noninvasive, repeated, low-cost imaging at ultra-high spatial resolution [ 27 ]. Our group and others have demonstrated the manifestation of AD pathological features in the retinas of asymptomatic individuals, those with mild cognitive impairment (MCI), and AD dementia patients, including Aβ deposits, vascular Aβ 40 and Aβ 42 , various aberrant tau isoforms, inflammation, vascular damage, and neurodegeneration [ 4 , 6 – 8 , 13 , 17 , 20 – 23 , 27 , 31 , 33 – 35 , 43 – 45 , 47 , 50 , 51 , 56 , 59 , 63 , 65 , 67 , 70 , 71 , 73 , 74 , 79 , 87 , 89 ].…”

“…Current limitations in early diagnosis and monitoring of AD in the clinical settings [ 3 , 41 ], make retinal imaging a potential solution due to its accessibility for noninvasive, repeated, low-cost imaging at ultra-high spatial resolution [ 27 ]. Our group and others have demonstrated the manifestation of AD pathological features in the retinas of asymptomatic individuals, those with mild cognitive impairment (MCI), and AD dementia patients, including Aβ deposits, vascular Aβ 40 and Aβ 42 , various aberrant tau isoforms, inflammation, vascular damage, and neurodegeneration [ 4 , 6 – 8 , 13 , 17 , 20 – 23 , 27 , 31 , 33 – 35 , 43 – 45 , 47 , 50 , 51 , 56 , 59 , 63 , 65 , 67 , 70 , 71 , 73 , 74 , 79 , 87 , 89 ]. Some pathological changes associated with AD, such as Aβ deposits, tau isoforms, vascular damage, and atrophy, were more frequently detected or had a greater impact in the superior temporal (ST) or inferior temporal (IT) retinal regions of AD patients compared to controls [ 7 , 20 , 31 , 43 , 44 , 47 , 50 , 74 ].…”