Background: Preclinical Alzheimer’s disease (pAD) is a term for patientswith AD-type pathology but cognition within normal limits for age. Thelack of clinical symptoms in such cases has been hypothesized to relate to“cognitive reserve”. The association of pAD with demographic, clinical,genetic, and other comorbid pathological features remains unknown. Fewdetailed neuropathological studies of pAD exist. Methods: The Universityof Kentucky Alzheimer’s Disease Center follows a large group of cogni-tively normal subjects that agree to undergo extensive longitudinal annualclinical evaluations and consent to brain autopsy at death. Since 1989, 153cognitively normal subjects have come to autopsy from this group. De-tailed neuropathological assessment includes presence of AD, cerebrovas-cular disease (CVD), and Lewy body disease (LBD) pathology. Results:All subjects were cognitively normal on last examination before death(mean time from last examination to death � one year). pAD in this groupwas defined by NIA-Reagan intermediate or high-likelihood of AD withoutclinical symptoms (n�31, 20%). Other classifications included patholog-ically normal (NIA-Reagan low or no-likelihood of AD, n�87), �-amyloidpredominant pathology (CERAD probable or definite, Braak stage II orlower, n�13), neurofibrillary tangle predominant pathology (CERAD pos-sible or no, Braak stage III or higher, n�23). No differences were seen forgender, education, MMSE, or ApoE �2 allele frequency between groups inthis analysis. Age was lower in the pathologically normal group(p�0.0005, t-test), and ApoE �4 allele frequency was higher in both pADand �-amyloid predominant cases (p�0.01, 2 test). The presence ofamyloid angiopathy was associated with preclinical AD (p�0.002,Kruskal-Wallis ANOVA). All other measures of CVD (large vessel orlacunar infarcts, atherosclerosis, arteriosclerosis, microvascular disease,hemorrhagic infarcts) did not differ between groups. Likewise, LBD pa-thology did not differ between groups (p�0.62, Kruskal-Wallis ANOVA).Conclusions: AD-type neuropathology is seen relatively often in cogni-tively normal elderly persons. Both advanced age and ApoE �4 status areassociated with pAD (as they are with AD). The lack of association of pADwith CVD or LBD suggests that AD develops independently of thesepathological processes, at least in the early preclinical stages of disease.

P4-156 THIAZIN RED IS A SENSITIVE AND ACCURATEMARKER FOR THE FAST DIAGNOSIS OFALZHEIMER’S DISEASE IN NONFIXED BRAINTISSUE IN TOUCH IMPRINTS PREPARATIONS

Jose Luna, Janneth Peralta-Ramirez, Raul Mena, Cinvestav, Mexico,Mexico. Contact e-mail: jluna@fisio.cinvestav.mx

Background: At the present, the neuropathological diagnosis of Alz-heimer’s disease requires long lasting aldehyde fixation, followed bythe use of silver staining techniques and immunohistochemistry. Al-though, these two techniques are sensitive and reproducible, the meth-odological standardization may sometimes be difficult. Over the lastyears, we have used a variety of tau immunological markers combinedto the dye Thiazin red (TR). This dye is an accurate marker to differ-entiate fibrillar from non fibrillar state of both amyloid-� and tauprotein in AD (Mena R, 1995.Acta Neuropathol. (3):433-45). The touchimprint cytology has been commonly used by pathologist for the rapiddiagnosis of diseases, such as tumors. This technique is also cheaperand offers fast results when compared with silver staining and immu-nohistochemistry. Methods: In the present study, we used TR as adiagnostic marker of AD in defrosted unfixed brain tissue and touchimprint. Our aim was to determine the accurate diagnosis of ADneuropathology based upon the detection of intra-and extracellulartangles and neuritic plaques in brain tissueUnfixed brain tissue wasdefrosted and immediately immersed in a 0.0001% of TR aqueoussolution by 15 min, at room temperature, in the dark. Then, sampleswere briefly rinsed with a PBS-buffered solution and gently touched ona cover glass. Mounted samples were observed with an epi-fluorescencemicroscope Control experiments included the use of Thioflavin-S stain-ing, fixed tissue and some double labeled material with TR and selectedtau markers. Results: Our results indicate that TR retains its strong

affinity for both tangles and plaques in unfixed tissue and imprintcytology. This information provides a potential use of TR as an accuratediagnostic tool for the rapid post-mortem diagnosis of AD neuropathol-ogy. Conclusions: This information provides a potential use of TR asan accurate diagnostic tool for the rapid post-mortem diagnosis of ADneuropathology. This work was financially supported by CONACyTgrant (No. 47630).

P4-157 NEUROFIBRILLARY TANGLES OF A�40 INALZHEIMER BRAINS

Pedro Pesini, Ana M. Lacosta, Manuel Sarasa, Araclon Biotech,Zaragoza, Spain. Contact e-mail: pedropesini@araclon.com

Background: The two principal landmarks of brains affected by Alzhei-mer’s disease are the extracellular beta-amyloid plaques containing A�

proteins and the intracellular neurofibrillary tangles containing hyperphos-phorilated tau protein. Methods: Immunohistochemistry with antibodiesagainst A�40, A�42 and tau proteins in brains from Alzheimer patiens atdifferent Braak and Braak stages. Results: In all cases of Alzheimerdisease there are neurons displaying neurofibrillary tangles containingA�40 protein. These neurons with A�40-decorated neurofibrillary tanglesare located in the entorhinal cortex and the hippocampus, those corticalareas first affected in Alzheimer’s disease from the earliest stages of thedisease. Antibodies against the A�42 protein marked brain plaques but notneurofibrillary tangles.

Conclusions: The great similarity between the pictures of neurofibrillarytangles immunostained with either tau antibodies or A�40 antibodiesstrongly suggests that A�40 may also act as a cytoskeleton-associatedprotein, at least during the process of Alzheimer disease.

P4-158 PRESERVATION OF SYNAPTIC NUMBERS INTHE PRECUNEUS ASSOCIATED WITH MILDCOGNITIVE IMPAIRMENT AND MILD-TO-MODERATE ALZHEIMER’S DISEASE

Stephen W. Scheff1, Doug A. Price1, Frederick A. Schmitt1,Elliott J. Mufson2, 1University of Kentucky, Lexington, KY, USA; 2RushUniversity, Chicago, IL, USA. Contact e-mail: sscheff@email.uky.edu

Background: Synaptic decline is a hallmark associated with variousregions of the neocortex and hippocampus in mild-moderate Alzhimer’sdisease (mAD). This loss in connectivity is believed to be the basis forcognitive impairments including those related to episodic memory. Theposterior medial parietal cortex (precuneus) is a tertiary cortical asso-ciation area involved in episodic memory, attention and sequentialprocessing, functions impaired early in the course of AD. The precu-

T716 Poster Presentations P4: