CLINICAL NEUROSCIENCE AND NEUROPATHOLOGY NEUROREPORT 0959-4965 & Lippincott Williams & Wilkins Vol 11 No 16 9 November 2000 3427 Tau epitopes in spinal cord neurofibrillary lesions in Chamorros of Guam M. L. Schmidt, R. Garruto, 1 J. Chen, V. M.-Y. Lee and J. Q. Trojanowski CA Center for Neurodegenerative Disease, Research, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania Medical School, 3rd Floor HUP-Maloney Bldg., 3600 Spruce Street, Philadelphia, PA 19104-4283; 1 Binghamton University, Department for Anthropology and Neurosciences, Binghamton, NY, USA CA Corresponding Author Received 25 July 2000; accepted 18 August 2000 We examined spinal cord sections from Guamanian Chamor- ros with or without amyotrophic lateral sclerosis or parkinson- ism–dementia complex using immunohistochemistry and antibodies to epitopes that span the length of tau to characterize the tau epitope profile of neurofibrillary tangles in these spinal cords. Most (16/20) spinal cords, including some from Chamorros without documented clinical disease, con- tained tangles with a tau epitope profile similar to the tangles found in the forebrain and brain stem of these patients. NeuroReport 11:3427–3430 & 2000 Lippincott Williams & Wilkins. Key words: Chamorros; Guam; Neurofibrillary lesions; Spinal cord; Tau epitopes INTRODUCTION A high incidence of parkinsonism–dementia complex (PDC) and amyotrophic lateral sclerosis (ALS) has been reported in the Chamorros of Guam and Rota in the Mariana Islands [1,2]. Guam PDC is characterized neuro- pathologically by numerous tau immunoreactive neuro- fibrillary tangles (NFTs) throughout the forebrain and brain stem with few amyloid plaques and Lewy bodies [1– 3]. NFTs in Guam PDC are formed by paired helical filaments (PHFs) composed of hyperphosphorylated tau (PHFtau) similar to NFTs in Alzheimer’s disease (AD) brains, but the distribution of NFTs differs in PDC and AD [1–5]. For example, NFTs are virtually absent in the AD spinal cord, but NFTs occur in the spinal cords of patients with Guam PDC or ALS and PDC (ALS/PDC) [6–9]. ALS in Chamorros is characterized by a loss of anterior horn cells (AHC) as well as Bunina bodies and ubiquitin-posi- tive inclusions in surviving AHC. In addition NFTs are a frequent feature in Chamorro ALS patients but not in ALS patients outside of Guam [6–8,10,11]. Here, we report studies of NFTs in the spinal cord of Chamorros to determine whether they contain tau epitopes similar to NFTs in the brains of AD and Guam ALS/PDC patients. MATERIALS AND METHODS Spinal cords from 20 Chamorros were studied here. Ten patients had PDC, one had ALS/PDC, six had ALS and 3 were without documented neurological disease during life (see Table 1 for a summary of the individuals and spinal cord levels studied here). The spinal cords were fixed in formalin, embedded in paraffin and cut into 6 ìm sections. One set of sections was stained using the Gallyas method [12], and the other sections were examined by immunohistochemistry as de- scribed previously [5,13,14]. However, to detect masked epitopes, some spinal cord sections were boiled for 10 min in a proprietary antigen unmasking solution (Vector Lab- oratories, Burlingame, CA) prior to immunohistochemistry, which enhanced tau immunoreactivity in the lesions found in these sections. The ABC kits were purchased from Vector Laboratories (Burlingame, CA) and diaminobenzi- dine was used as chromogen as described [14]. The panel of epitope specific anti-tau antibodies used here has been characterized extensively (see [2,5,13,14] for details and additional citations). Polyclonal antibody 17026 was raised to recombinant tau and polyclonal N-tau recognizes the extreme amino terminal of tau. The other seven antibodies recognize epitopes containing phosphorylated threonines and/or serines between amino acids 181 and 404 of the tau molecule. The controls and analytical methods used here were similar to those reported earlier [14], and representa- tive illustrations of the findings reported here were pre- pared with a DC-330 video camera (DAGE-MTI, Inc Michigan City, IN) mounted on a Nikon FXA microscope. The figure was printed on a Fuji Pictrography 3000 printer. RESULTS The detailed observations of the Gallyas- and the immuno- histochemical-stained sections are summarized in Table 1. All of the PDC patients had many Gallyas- and tau- positive spinal cord NFTs, while four of the six ALS patients (numbers 11, 13, 14, 16), the PDC/ALS patients