Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc.
In prion-related encephalopathies, microglial activation occurs early and is dependent on accumulation of disease-specific forms of the prion protein (PrPSc) and may play a role in nerve cell death. Previously, we found that different types of PrPSc (i.e. type 1 and type 2) coexisted in approximately 25% of patients with sporadic Creutzfeldt-Jakob disease (CJD); and a close relationship was detected between PrPSc type, the pattern of PrP immunoreactivity, and extent of spongiform degeneration. To investigate whether microglial reaction is related to the biochemical type and deposition pattern of PrPSc, we carried out a neuropathologic and biochemical study on 26 patients with sporadic CJD, including all possible genotypes at codon 129 of the prion protein gene. By quantitative analysis, we demonstrated that strong microglial activation was associated with type 1 PrPSc and diffuse PrP immunoreactivity, whereas type 2 PrPSc and focal PrP deposits were accompanied by mild microglia reaction. These findings support the view that the phenotypic heterogeneity of sporadic CJD is largely determined by the physicochemical properties of distinct PrPSc conformers.
Puoti
Gianfranco
G
Istituto Nazionale Neurologico Carlo Besta, Milano, and Dipartimento di Scienze Neurologiche, Seconda Università di Napoli, Napoli, Italy.
Giaccone
Giorgio
G
Mangieri
Michela
M
Limido
Lucia
L
Fociani
Paolo
P
Zerbi
Pietro
P
Suardi
Silvia
S
Rossi
Giacomina
G
Iussich
Selina
S
Capobianco
Raffaella
R
Di Fede
Giuseppe
G
Marcon
Gabriella
G
Cotrufo
Roberto
R
Filippini
Graziella
G
Bugiani
Orso
O
Tagliavini
Fabrizio
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D018620:PrPSc Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D018620:PrPSc Proteins; D020033:Protein Isoforms