Microtubule-associated tau protein positive neuronal and glial inclusions in ALS.
BACKGROUND
The authors compared tau protein deposition in the frontal cortex of patients with cognitive impairment of amyotrophic lateral sclerosis (ALSci) (n = 6), cognitively intact patients with ALS (n = 6), and age-matched controls (n = 6) in order to determine the pathologic substrate of ALSci.


METHODS
Archival paraffin-embedded tissue was examined using Gallyas staining and immunostaining for tau-1 (phosphorylation-dependent tau epitope), tau-2 (phosphorylation independent), Alzheimer-specific tau phosphoepitopes (AT 8; ser(396) phosphorylation), beta-amyloid, glial fibrillary acid protein, SMI 31 (recognizing phosphorylated NFH), alpha-synuclein, or ubiquitin.


RESULTS
Tau immunoreactive astrocytic and dense neuronal inclusions were found in both ALS and ALSci, although to a greater extent in ALSci. Superficial linear spongiosis and Gallyas-positive intraneuronal aggregates, immunoreactive with tau-1 and AT 8 but rarely to ser(396) tau, were unique to ALSci. Dense extracellular aggregates were observed by both Gallyas staining and tau-1 immunostaining. Tufted degenerating astrocytes containing tau-1 and AT 8 immunoreactive aggregates and, rarely, dense Gallyas positive neuritic plaques immunoreactive with tau-1 and AT 8, but not with ser(396) tau or beta-amyloid, were observed in ALSci. Tau positive glial coiled bodies were observed in the deep cortical layers and adjacent subcortical white matter in ALSci. Although 3R and 4R tau mRNA isoforms were expressed to similar levels in the frontal cortex of all cases, the total amount of tau mRNA was increased in both ALS and ALSci. Both gray and white matter soluble tau protein expression was similar among control, ALS, and ALSci cases.


CONCLUSIONS
Cognitive dysfunction in ALS may reflect abnormal tau protein metabolism.
Yang
Wencheng
W
Robarts Research Institute, The University of Western Ontario, London, Canada.
Sopper
Maggie M
MM
Leystra-Lantz
Cheryl
C
Strong
Michael J
MJ
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000473:pathology*; D000918:Antibody Specificity; D015153:Blotting, Western; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology*; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology* / Q000648:ultrastructure; D008875:Middle Aged; D009457:Neuroglia / Q000737:chemistry / Q000473:pathology*; D009474:Neurons / Q000737:chemistry / Q000473:pathology*; D019581:Neuropil / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D016875:tau Proteins / Q000032:analysis* / Q000235:genetics
D012333:RNA, Messenger; D016875:tau Proteins