Patterns of Tau and α-Synuclein Pathology in the Visual System.
BACKGROUND
Spreading of misfolded proteins has been suggested for neurodegenerative diseases. The hierarchical distribution of protein deposits in Alzheimer's (AD) and Parkinson's disease (PD) supports this concept.


OBJECTIVE
To evaluate α-synuclein and tau-deposition in the optic pathway as an excellent anatomical model, which follows a strict trajectory including a cortico-geniculate feedback connection.


METHODS
We immunostained the optic nerve, lateral geniculate nucleus (LGN), and occipital cortex for AT8 (phosphorylated tau), α-synuclein, and disease-associated prion protein (PrP) in 47 cases with tau pathology (AD type, argyrophilic grain disease, or progressive supranuclear palsy), 16 PD, and 5 Creutzfeldt-Jakob disease (CJD) cases, respectively.


RESULTS
We detected immunoreactivity for all proteins along the optic pathway. The optic nerve showed immunopositivity only in cases with tau (6/8, 75%) or α-synuclein (5/7, 71%) pathology. The LGN was involved also frequently (tau: 22/47, 46.8% ; α-synuclein: 15/16, 93.7% ; PrP 5/5, 100%). The occipital cortex was variably affected by tau or α-synuclein pathology, but always showed PrP immunoreactivity in the CJD cases. Tau pathology in the LGN correlated with tau immunoreactivity in the occipital cortex and Braak stages of neurofibrillary degeneration. In tauopathies, which do not involve the occipital cortex, like argyrophilic grain disease or progressive supranuclear palsy, tau pathology was more frequently astrocytic in the LGN.


CONCLUSIONS
Our results have implications 1) for the understanding of disease spreading along neural pathways and 2) for the diagnostic evaluation of the visual system in neurodegenerative proteinopathies as a potential biomarker to evaluate disease progression or subgrouping of cases.
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Jasmin
J
Rahimi
Institute of Neurology, Medical University of Vienna, Vienna, Austria.|Department of Clinical Neurology, Medical University of Vienna, Vienna, Austria.
Ivan
I
Milenkovic
Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Gabor G
GG
Kovacs
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology; D005829:Geniculate Bodies / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D016874:Neurofibrillary Tangles; D009778:Occipital Lobe / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011328:Prions / Q000378:metabolism; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D014795:Visual Pathways / Q000378:metabolism* / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
C054369:MAPT protein, human; D011328:Prions; D051844:alpha-Synuclein; D016875:tau Proteins
Lateral geniculate body; neurodegeneration; prion protein; prion-like spreading; tau; visual system; α-synuclein