Gerstmann-Str�ussler syndrome ? A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Abstract

This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti-beta protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.

An autopsy report of three kindred in a Gerstmann–Sträussler–Scheinker disease P105L family with a special reference to prion protein, tau, and beta‐amyloid

“…Although the clinical picture of GSS105 is usually predominated by gait disturbance (spastic paraparesis), psychiatric symptoms, and dementia (Amano et al, ; Isshiki et al, ; Itoh et al, ; Kitamoto, Amano, et al, ; Kubo et al, ; Nakazato et al, ; Yamada et al, ), there is a substantial variation to it even within the same family (Iwasaki, Kizawa, Hori, Kitamoto, & Sobue, ; Koshi Mano et al, ; Shiraishi, Mizusawa, & Yamada, ; Yamada et al, ; Yamazaki et al, ). In a GSS105 family reported elsewhere (Shiraishi et al, ; Yamazaki et al, ), one member presented with gait disturbance (gait apraxia) that was followed by mutism (Yamazaki et al, ), and the other presented with sensory and psychiatric symptoms, including a persistent complaint of pains in various parts of the body, which were then followed by memory disturbance, delusion, and gait disturbance (Shiraishi et al, ).…”

“…GSS is clinically characterized by a constellation of signs and symptoms, and the cardinal neuropathological feature of GSS is the formation of amyloid plaques composed of PrP (PrP‐plaques) that are most abundant in the cerebral cortex, basal ganglia, and cerebellar cortex (Ghetti et al, ). GSS P105L (GSS105), a rare variant of GSS caused by a point mutation of PRNP at codon 105 (proline to leucine substitution), was first reported in Japan (Kitamoto, Amano, et al, ; Yamada et al, ) and is clinically characterized by gait disturbance (spastic paraparesis), dementia, or psychiatric disorders (Amano et al, ; Isshiki, Minagawa, & Yamauchi, ; Itoh et al, ; Kitamoto, Amano, et al, ; Kubo, Nishimura, Shikata, Kokubun, & Takasu, ; Nakazato, Ohno, Negishi, Hamaguchi, & Arai, ; Yamada et al, ).…”

Tau, prions and Aβ: the triad of neurodegeneration

“…The first reports were those of classical GSS with the PRNP P102L mutation [5, 8, 34, 35, 73, 89]. Later studies of P102L GSS with detection of abundant phospho-tau concluded that this may be an effect of PrP-mediated phosphorylation rather than a Aβ related effect, as there were only minimal Aβ deposits seen [52].…”

Coexistence of CJD and Alzheimer's disease: An autopsy case showing typical clinical features of CJD

“…Human prion disease includes three major groups: (i) acquired (Kuru, iatrogenic CJD, and new variant CJD); (ii) sporadic CJD, sporadic fatal insomma, and (iii) inherited, which encompasses the familial form of CJD, the GSS syndrome, and fatal familial insomnia. [1][2][3][4][5][6][7][8][9][10][11] Sporadic CJD is a rare neurodegenerative disorder clinically characterized by rapidly worsening dementia with myoclonus, extrapyramidal signs, and cerebellar signs, and pathologically showing spongiform change, neuronal loss, astrocytosis, and abnormal prion protein deposition in the brain. [12][13][14][15][16][17][18][19][20][21] It is well known that coexistence of pathological features of CJD and Alzheimer's disease (AD) in the same patient or the same family has been rarely demonstrated.…”