Carlos Augusto Pasquallucci

Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's Disease

Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht‐NCI) are the best protein correlate of clinical decline in Alzheimers disease (AD). Qualitative evidence identifies ht‐NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht‐NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages.

APOPTOSIS AND AUTOPHAGY CHANGES CORRELATE WITH ALZHEIMER'S DISEASE PROGRESSION IN HUMANS: A STEREOLOGICAL POSTMORTEM STUDY

in the limbic system and progressively spreads into primary processing and sensory regions such as the primary visual cortex and the retina. For the first time, here we assess the propagation of Ab42 peptide-mediated amyloidogenesis and pro-inflammatory gene expression (at the level of miRNA, mRNA and protein) in the neocortical-thalamic-retinal visual pathway of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum (sulfate). Methods:5xFAD Tg-AD murine models, RNA sequencing, GeneChip (microRNA and mRNA), RT-PCR, LED-Northern, Western, ELISA and bioinformatics analysis. Results:The three most significant findings were (i) in aluminum-supplemented animals, markers for inflammatory neuropathology appeared in both the brain and the retina as evidenced by an evolving presence of Ab42 peptides; (ii) increases in Ab42 peptide abundance in these animals were accompanied by the up-regulation of several pro-inflammatory markers including cyclooxygenase-2 (COX-2) and C-reactive protein (CRP); and (iii) that as similarly reported in other Tg-AD murine models, there was a significantly accelerated development of Ab42-mediated inflammatory neuropathology in 5xFAD Tg-AD mice fed aluminum. Conclusions: Taken together the results indicate that in the 5xFAD Tg-ADmodel aluminum not only enhances an Ab42-mediated inflammatory neurodegeneration in the brain but also significantly induces AD-type neuropathology in anatomically-linked primary sensory areas that involve the acquisition and processing of visual signals.

AGING RELATED TAU ASTROGLIOPATHY AND ITS IMPACT ON GREY MATTER

protocol including 3D-T1w, T2wmFLAIR and DTI imaging (2), a radiological report including assessment of atrophy, white matter hyperintensities and infarcts of the in situ MRI by an experienced radiologist (3), initial preprocessing of data such as SIENAX and FIRST and registration with other imaging modalities (4), ex-vivo 7T MRI including 3D-T1, FLAIR, T2 and SWI (5). At brain dissection collection of snap-frozen and fixed brain tissue (7), from the latter tissue blocks are used for a full pathological assessment (7), MRI and (immune)histopathology data are analysed using morphometry and stereology (8). Poster Presentations: Monday, July 23, 2018 P908

EDUCATION AND COGNITIVE RESERVE: A CLINICO-PATHOLOGICAL STUDY FROM THE BRAZILIAN AGING BRAIN STUDY GROUP

had a 67% decreased risk of hospitalization and a 50% decreased risk of ERV. A comparator was hospitalized for C. difficile diarrhea diagnosis and treatment, whereas an intervention subject with the same diagnosis avoided hospitalization. One intervention subject recovered the ability to walk through memory coaching, after a serious hip fracture secondary to osteoporosis and a fall. A comparator woke-up, wandered, fell, was hospitalized with a pelvic fracture, and subsequently unable to walk. Successful replication and dissemination of CI-PCM program results could result in significantly reduced AD care costs and greatly improved AD patient care.

NEUROPATHOLOGICAL FINDINGS OF AN EARLY-ONSET DEMENTIA CASE WITH ATYPICAL ALZHEIMER’S DISEASE: HOW CHALLENGING CAN THE CLINICAL DIAGNOSIS OF MIXED AD BE?

P1-359 NEUROPATHOLOGICAL FINDINGS OFAN EARLY-ONSET DEMENTIA CASE WITH ATYPICAL ALZHEIMER’S DISEASE: HOW CHALLENGING CAN THE CLINICAL DIAGNOSIS OF MIXED AD BE? Roberta Diehl Rodriguez, Mariana Molina, Renata P. Leite, Rafaela Sabadin, Leonel Tadao Takada, Claudia K. Suemoto, Wilson Jacob-Filho, Leila Chimelli, Carlos Augusto Pasquallucci, Lea Tenenholz Grinberg, Ricardo Nitrini, University of S~ao Paulo Medical School, S~ao Paulo, Brazil; Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Contact e-mail: robertadiehlr@gmail.com

THE CONTRIBUTION OF HYPERPHOSPHORYLATED-TAU PATHOLOGY TO NEUROPSYCHIATRIC SYMPTOMS IN ALZHEIMER’S DISEASE

immigrants. Methods: 49 Moroccan, Turkish and Cape Verdean patients with diverse cognitive complaints visited the multicultural memory clinic of the Alzheimer Center Rotterdam, TheNetherlands. 35% of the patients were illiterate; 71% did not complete primary education. An adapted test protocol including the Cross Cultural Dementia screening test (CCDz) was used, as well as Dutch neuropsychological tests that are considered cross-culturally applicable. A medical interpreter translated the test instructions. Results: Nearly all patients could complete the recognition memory task of the CCD, a test that is not timed and contains culture-sensitive photographs. 24% of patients were unable to finish the CCD’s timed task involving dot counting (similar to TMT A); 60% of all patients were unable to complete the combined counting/switching task. Most of the other cognitive tests required too many scholastic skills and abstract reasoning (e.g. figure copy, digit span, BADS key search test) andwere therefore not even attemptedwithmany patients. Qualitative analysis of the results revealed difficulties in recognizing line drawings (e.g. visual-associative memory), drawing linear designs and processing depth cues. Similarly, tests relying heavily on verbal responses and vocabulary (such as naming tasks, verbal memory, orientation questions) often were not administered. Conclusions: In the memory clinic, neuropsychological assessments requiring basic scholastic skills, involving line drawings and relying heavily on language/vocabulary are unfit for use in linguistically and culturally diverse populations. Adapting stimuli to include life-like material (e.g. photographs)might be promising.Our future researchwill focus on the development of cross-cultural testsmeasuring all cognitive domains. z Goudsmit et al. 2016 J Clin Exp Neuropsychol.

THE SUBCORTICAL SEROTONERGIC DORSAL RAPHE'S LINK TO PROGRESSIVE ALZHEIMER'S DISEASE

O3-04-01 THE SUBCORTICAL SEROTONERGIC DORSAL RAPHE’S LINK TO PROGRESSIVE ALZHEIMER’S DISEASE Austin K. Nguy, Alexander J. Ehrenberg, Panos Theofilas, Sara Dunlop, Ana T. Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Maria B. Mejia, Claudia K. Suemoto, JoseM. Farfel, Renata Eloah de Lucena Ferretti-Rebustini, Livia Polichiso, Camila F. Nascimento, William W. Seeley, Ricardo Nitrini, Carlos Augusto Pasquallucci, Wilson Jacob-Filho, Udo Rueb, Helmut Heinsen, Lea T. Grinberg, University of California, Berkeley, Berkeley, CA, USA; 2 University of California, San Francisco, San Francisco, CA, USA; Hospital Albert Einstein, S~ao Paulo, Brazil; 4 University of S~ao Paulo Medical School, S~ao Paulo, Brazil; 5 University of S~ao Paulo, School of Nursing, S~ao Paulo, Brazil; University of Sao Paulo Medical School, Sao Paulo, Brazil; University of Table 1 Assosiation of grey matter voxels to specific cognitive domains. Number in cell represents the cluster size of significant voxels in specific brain region. Clusters formed based on p-value threshold 3x10 estimated from permutations.

Locus ceruleus volume changes are a promising biomarker for detecting Alzheimer's disease progression in pre-symptomatic stages

with non-fluent variant primary progressive aphasia showed asymmetric binding in the left inferior frontal and parietal cortex (Figure 2). Tracer binding was unexpectedly seen in all 3 patients with FTD due to presumed tau-negative, TDP43-posistive inclusions, particularly in degenerating white matter (Figure 3). 1/2 patients at risk for CTE showed focal AV1451 binding in the left anterior temporal lobe (Figure 4). Conclusions:AV1451 uptake largely conformed to the expected distribution of pathology in non-AD tauopathies, though subcortical signal overlapped with binding in NC. Unexpected AV1451 uptake was also found in patients with presumed tau-negative, FTD-TDP pathology. PET-to-autopsy correlation studies are needed to better characterize these findings.

Determination of related factors for the nursing diagnosis ‘chronic confusion’ by brain autopsy

medial temporal allocortex. A stage model of progressing amyloid pathology was derived by grouping regions into four equallyspaced divisions from highest to lowest frequency (Figure 1). Examination of individual amyloid deposition profiles confirmed that amyloid deposition in the four cortical divisions was nested across subjects, and only 3 out of 111 subjects with detectable amyloid pathology were found to deviate from the staging scheme (Figure 2). Higher cortical amyloid stages were associated with advanced age (Spearman’s r1⁄40.23, p1⁄40.02), APOE4 carrier status (r1⁄40.23, p1⁄40.01), and worse delayed recall performance (r1⁄4-0.34, p<0.001). In unbiased training-test analyses assessing the consistency of the extrapolated staging scheme across individuals, on average 4666% of the test subjects showed amyloid deposition in any of the 4 cortical divisions and in 9165% of these the deposition pattern conformed to the model of nested stages derived from the training data. Conclusions:The nested stages of regional PET-evidenced amyloid pathology across cognitively normal subjects resemble previous neuropathological observations and suggest a largely consistent progression pattern of cortical amyloid deposition during the preclinical phase of AD.

Lc caudal cells show the earliest vulnerability to Alzheimer's disease

46.4% had low likelihood AD and only 3.8% had intermediate or high likelihood AD. The frequency of AD pathology increased linearly with age (p<0.01) (Figure 1). Ninety-four subjects (51.9%) were free of NFTs and another 78 (43.1%) only had a Braak Stage I or II. Only 8.9% of the sample had neuritic plaques. In the subgroup 50-54 years old (24.3%) we could not find any subject with moderate or high likelihood for pathologic AD. The youngest person with moderate likelihood for pathologic AD was 61 years old. Microinfacrts and small vessel disease were found in 15.9% and 24.7% of the sample, respectively. Lewy bodies were identified in only 2.7% of the sample. Age was not associated to non-AD neuropathologic indices. Conclusions: In a community based sample of persons 50-64 years old, intermediate or high likelihood neuropathologic AD is rare before the age of 60.