Hart NJ, Koronyo Y, Black KL, Koronyo-Hamaoui M.
Ocular indicators of Alzheimer's: exploring disease in the retina.
Acta Neuropathol. 2016 Dec;132(6):767-787. Epub 2016 Sep 19
PubMed.
The findings by the Koronyo-Hamaoui lab showed that retinas of Alzheimer’s disease patients exhibit some of the key features associated with the disease, inlcuding deposition of amyloid plaques and tau aggregates, as well as tissue degeneration. The retina is unique in that it is the only CNS tissue that is readily accessible for noninvasive imaging that does not require the use of elaborate tracers, such as those needed to conduct 18F-PET, inter alia. These insights open up a fundamentally novel avenue to study the pathophysiology of AD in vivo and screen populations at risk of developing AD. See also LaMorgia et al., 2016.
References:
La Morgia C, Ross-Cisneros FN, Koronyo Y, Hannibal J, Gallassi R, Cantalupo G, Sambati L, Pan BX, Tozer KR, Barboni P, Provini F, Avanzini P, Carbonelli M, Pelosi A, Chui H, Liguori R, Baruzzi A, Koronyo-Hamaoui M, Sadun AA, Carelli V.
Melanopsin retinal ganglion cell loss in Alzheimer disease.
Ann Neurol. 2016 Jan;79(1):90-109. Epub 2015 Dec 18
PubMed.
Multicenter studies with enforced blinding of results assessment will be necessary to resolve the discrepancies in reports from different labs. As mentioned in this paper, a very well respected Johns Hopkins group (Ho et al., 2013) found no evidence for either Aβ or tau pathology in the retina or lens of AD subjects. More recently, another respected group at Massachusetts General Hospital led by Matthew Frosch, Brad Hyman, and Anat Stemmer-Rachamimov reported similarly negative findings at the 2016 meeting of the American Association of Neuropathologists. Our own unpublished findings, on immunohistochemical staining of AD and control retinal wholemounts, concur with these negative reports.
References:
Ho CY, Troncoso JC, Knox D, Stark W, Eberhart CG.
Beta-Amyloid, Phospho-Tau and Alpha-Synuclein Deposits Similar to Those in the Brain Are Not Identified in the Eyes of Alzheimer's and Parkinson's Disease Patients.
Brain Pathol. 2013 May 29;
PubMed.
We read this report with interest, but have to state that, similar to Thomas Beach, we did not observe evidence for amyloid pathology in the retina of AD subjects nor in the retinas of amyloid mouse models (Schön et al., 2012). We failed to publish these negative results in Acta Neuropathologica in 2011. We were only able to observe fibrillar tau in the retina of tau transgenic mice.
We propose as possible explanation(s) the fact that only a (small) sub-group of AD patients is concerned, or that they suffer from a confounding pathology, or that the data are a technical or interpretational artifact. For example, the Aβ antibody concentration commonly used to stain plaques in the brain is much lower than what Koronyo-Hamaoui used for detecting amyloid in the retina.
It is in the best interest of all concerned, not the least that of AD patients and their relatives, that the Koronyo-Hamaoui group makes available their raw data and materials to allow others to decide why renowned labs throughout the world have been unable to confirm their findings on retina amyloid pathology in AD patients.
References:
Schön C, Hoffmann NA, Ochs SM, Burgold S, Filser S, Steinbach S, Seeliger MW, Arzberger T, Goedert M, Kretzschmar HA, Schmidt B, Herms J.
Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice.
PLoS One. 2012;7(12):e53547.
PubMed.
Comments
UCSC
The findings by the Koronyo-Hamaoui lab showed that retinas of Alzheimer’s disease patients exhibit some of the key features associated with the disease, inlcuding deposition of amyloid plaques and tau aggregates, as well as tissue degeneration. The retina is unique in that it is the only CNS tissue that is readily accessible for noninvasive imaging that does not require the use of elaborate tracers, such as those needed to conduct 18F-PET, inter alia. These insights open up a fundamentally novel avenue to study the pathophysiology of AD in vivo and screen populations at risk of developing AD. See also LaMorgia et al., 2016.
References:
La Morgia C, Ross-Cisneros FN, Koronyo Y, Hannibal J, Gallassi R, Cantalupo G, Sambati L, Pan BX, Tozer KR, Barboni P, Provini F, Avanzini P, Carbonelli M, Pelosi A, Chui H, Liguori R, Baruzzi A, Koronyo-Hamaoui M, Sadun AA, Carelli V. Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann Neurol. 2016 Jan;79(1):90-109. Epub 2015 Dec 18 PubMed.
Banner Sun Health Research Institute
Multicenter studies with enforced blinding of results assessment will be necessary to resolve the discrepancies in reports from different labs. As mentioned in this paper, a very well respected Johns Hopkins group (Ho et al., 2013) found no evidence for either Aβ or tau pathology in the retina or lens of AD subjects. More recently, another respected group at Massachusetts General Hospital led by Matthew Frosch, Brad Hyman, and Anat Stemmer-Rachamimov reported similarly negative findings at the 2016 meeting of the American Association of Neuropathologists. Our own unpublished findings, on immunohistochemical staining of AD and control retinal wholemounts, concur with these negative reports.
References:
Ho CY, Troncoso JC, Knox D, Stark W, Eberhart CG. Beta-Amyloid, Phospho-Tau and Alpha-Synuclein Deposits Similar to Those in the Brain Are Not Identified in the Eyes of Alzheimer's and Parkinson's Disease Patients. Brain Pathol. 2013 May 29; PubMed.
Ludwig-Maximilians-Universität Munich
We read this report with interest, but have to state that, similar to Thomas Beach, we did not observe evidence for amyloid pathology in the retina of AD subjects nor in the retinas of amyloid mouse models (Schön et al., 2012). We failed to publish these negative results in Acta Neuropathologica in 2011. We were only able to observe fibrillar tau in the retina of tau transgenic mice.
We propose as possible explanation(s) the fact that only a (small) sub-group of AD patients is concerned, or that they suffer from a confounding pathology, or that the data are a technical or interpretational artifact. For example, the Aβ antibody concentration commonly used to stain plaques in the brain is much lower than what Koronyo-Hamaoui used for detecting amyloid in the retina.
It is in the best interest of all concerned, not the least that of AD patients and their relatives, that the Koronyo-Hamaoui group makes available their raw data and materials to allow others to decide why renowned labs throughout the world have been unable to confirm their findings on retina amyloid pathology in AD patients.
References:
Schön C, Hoffmann NA, Ochs SM, Burgold S, Filser S, Steinbach S, Seeliger MW, Arzberger T, Goedert M, Kretzschmar HA, Schmidt B, Herms J. Long-term in vivo imaging of fibrillar tau in the retina of P301S transgenic mice. PLoS One. 2012;7(12):e53547. PubMed.
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