Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies
Manuela Neumann, Philipp J. Kahle, Benoit I. Giasson, Laurence Ozmen, Edilio Borroni, Will Spooren, Veronika Müller, Sabine Odoy, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, John Q. Trojanowski, Hans A. Kretzschmar, Christian Haass
Manuela Neumann, Philipp J. Kahle, Benoit I. Giasson, Laurence Ozmen, Edilio Borroni, Will Spooren, Veronika Müller, Sabine Odoy, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, John Q. Trojanowski, Hans A. Kretzschmar, Christian Haass
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Article Neuroscience

Misfolded proteinase K–resistant hyperphosphorylated α-synuclein in aged transgenic mice with locomotor deterioration and in human α-synucleinopathies

Abstract

Research Article

Authors

Manuela Neumann, Philipp J. Kahle, Benoit I. Giasson, Laurence Ozmen, Edilio Borroni, Will Spooren, Veronika Müller, Sabine Odoy, Hideo Fujiwara, Masato Hasegawa, Takeshi Iwatsubo, John Q. Trojanowski, Hans A. Kretzschmar, Christian Haass

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Age-dependent formation of PK-resistant αS in transgenic mice. (a) αS PK...
Age-dependent formation of PK-resistant αS in transgenic mice. (a) αS PK-PET blots of an 11-month-old heterozygous (het) mouse showed no PK-resistant αS. (b) βS PK-PET blots of a 24-month-old heterozygous mouse showed no PK-resistant βS (+PK) despite strong staining of PK-labile βS (–PK). (c and d) PK-PET blots of a 24-month-old heterozygous mouse before (c) and after (d) PK treatment showed specific staining of PK-resistant αS only in specific brain regions, although transgenic αS was expressed throughout the brain. (e) The same pathology was already seen on αS PK-PET blots of a 9-month-old homozygous (hom) mouse. (f) αS PK-PET blot of the SC of an 8-month-old homozygous mouse. (g and h) Higher magnifications of the areas boxed in e, namely cortex (g) and pontine reticular field (h). Scale bar in a, 5 mm (a–e); in f, 1 mm; in g, 200 μm (g and h). Numbers in d and f: 1, hippocampus; 2, thalamus; 3, zona incerta; 4, aqueduct and periaqueductal gray; 5, superior colliculus; 6, mesencephalic nucleus; 7, SN; 8, cerebellum; 9, facial nerve root; 10, pontine zona reticulata; 11, nucleus of solitary tract; 12, aqueduct; 13, hypoglossal nucleus; 14, medullary zona reticulata; 15, pyramidal tract; 16, ventral horn; 17, dorsal horn; 18, dorsal columns.