Distinct Pathological Features of the Gallyas- and Tau-positive Glia in the Parkinsonism-Dementia Complex and Amyotrophic Lateral Sclerosis of Guam

Neuropathology of parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam: an update

“…Granular hazy inclusions were observed in the astrocytes in the amygdaloid nucleus, motor cortex, and inferior olivary nucleus (Fig. 3a, b) [31]. Crescent/coiled inclusions were present in the oligodendroglia of the anterior nucleus of the thalamus, motor cortex, midbrain tegmentum, and the pyramids (Fig.…”

On the ‘classification’ of neurodegenerative disorders: discrete entities, overlap or continuum?

“…In some disorders, a direct link has been postulated between the presence of a specific gene mutation and the formation of a 'signature' brain lesion. Hence, mutations of the amyloid precursor protein (APP) [31,54] and presenilin (PSEN) genes PSEN1 [126] and PSEN2 [86], have been linked to familial forms of AD (FAD), the tau gene (MAPT) to FTD with parkinsonism linked to chromosome 17 (FTDP-17) [119], and α-synuclein [143], leucine-rich repeat kinase 2 (LRRK2) [143], and PARK7 (DJ-1) [112] genes to familial forms of Parkinson's disease (PD). In addition, the majority of familial cases of FTLD with ubiquitin-immunoreactive and tau-negative inclusions (FTLD-U), are associated with mutations of the progranulin (GRN) gene [21,24,33,102,118], with smaller numbers of cases associated with valosin-containing protein (VCP) gene mutation [47] or variants in the ubiquitin associated binding protein 1 (UBAP1) gene [93,121].…”

“…Tau is antigenically similar in several of the tauopathies [127] and a number of classifications have been proposed most notably by Trojanowski and Dickson [137] and Cairns et al [29]. Nevertheless, the different molecular isoforms of tau do not exhibit high fidelity, 4-repeat (4R) tau occurs in AD, CBD, PSP, FTDP-17 as well as FTLD-MND, AGC, and the parkinsonism dementia complex of Guam (PDC-G) [97] while 3-repeat (3R) tau is present in AD, PiD, and PDC-G. Tau-immunoreactive GI have also been found in ALS with dementia [146], FTDP-17 [119], PiD [120], CBD, PSP, parkinsonism-dementia complex and ALS of Guam (ALS/PDC) [112], and in a few cases of MSA [131].…”

Glial cell inclusions and the pathogenesis of neurodegenerative diseases

“…Less frequently, tau-positive glial inclusions are detected in Guam Parkinson-dementia complex (Oyanagi et al, 1997), post-encephalitic Parkinsonism and other neurodegenerative disorders that contain NFTs. Tau-positive astrocytic lesions are found in AD and in the aged human brain in the form of, so-called, 'thorn-shaped astrocytes' (Ikeda et al, 1995), but these lesions, which are relatively restricted to the white matter of the medial temporal lobe and the periventricular and subpial regions in the basal forebrain, are not clinically significant and are of no diagnostic importance.…”