Physical Sciences and Mathematics Commons^™

Machine Learning Approaches In Comparative Studies For Alzheimer’S Diagnosis Using 2d Mri Slices, Zhen Zhao, Joon Huang Chuah, Chee-Onn Chow, Kaijian Xia, Yee Kai Tee, Yan Chai Hum, Khin Wee Lai

Turkish Journal of Electrical Engineering and Computer Sciences

Alzheimer’s disease (AD) is an illness that involves a gradual and irreversible degeneration of the brain. It is crucial to establish a precise diagnosis of AD early on in order to enable prompt therapies and prevent further deterioration. Researchers are currently focusing increasing attention on investigating the potential of machine learning techniques to simplify the automated diagnosis of AD using neuroimaging. The present study involved a comparison of models for the detection of AD through the utilization of 2D image slices obtained from magnetic resonance imaging brain scans. Five models, namely ResNet, ConvNeXt, CaiT, Swin Transformer, and CVT, were implemented …

Oxidative Stress In Health And Disease, V. Prakash Reddy

Chemistry Faculty Research & Creative Works

Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other …

Disease Progression Modelling Of Alzheimer's Disease Using Probabilistic Principal Components Analysis, Martin Saint-Jalmes, Victor Fedyashov, Daniel Beck, Timothy Baldwin, Noel G. Faux, Pierrick Bourgeat, Jurgen Fripp, Colin L. Masters, Benjamin Goudey

Natural Language Processing Faculty Publications

The recent biological redefinition of Alzheimer's Disease (AD) has spurred the development of statistical models that relate changes in biomarkers with neurodegeneration and worsening condition linked to AD. The ability to measure such changes may facilitate earlier diagnoses for affected individuals and help in monitoring the evolution of their condition. Amongst such statistical tools, disease progression models (DPMs) are quantitative, data-driven methods that specifically attempt to describe the temporal dynamics of biomarkers relevant to AD. Due to the heterogeneous nature of this disease, with patients of similar age experiencing different AD-related changes, a challenge facing longitudinal mixed-effects-based DPMs is the …

Longitudinal Changes In Alzheimer’S-Related Plasma Biomarkers And Brain Amyloid, Murat Bilgel, Abhay Moghekar, Henrik Zetterberg, Bruno Jedynak, Multiple Additional Authors

Mathematics and Statistics Faculty Publications and Presentations

Introduction Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer’s progression assessment strategies.

Methods We examined the temporal order of changes in plasma amyloid-β ratio (Aβ42/Aβ40), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios (p-tau181/Aβ42, p-tau231/Aβ42) relative to 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB−/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1-year follow-up.

Results PiB groups exhibited different rates of longitudinal change in Aβ42/Aβ40 (β = 5.41 × 10-4, SE = 1.95 × 10-4, p = 0.0073). …

Rage Inhibitors In Neurodegenerative Diseases, V. Prakash Reddy, Puspa Aryal, Pallavi Soni

Chemistry Faculty Research & Creative Works

Nonenzymatic Reactions of Reducing Sugars with Primary Amino Groups of Amino Acids, Proteins, and Nucleic Acids, Followed by Oxidative Degradations Would Lead to the Formation of Advanced Glycation Endproducts (AGEs). the AGEs Exert Multifactorial Effects on Cell Damage Leading to the Onset of Neurological Disorders. the Interaction of AGEs with the Receptors for Advanced Glycation Endproducts (RAGE) Contribute to the Activation of Intracellular Signaling and the Expression of the Pro-Inflammatory Transcription Factors and Various Inflammatory Cytokines. This Inflammatory Signaling Cascade is Associated with Various Neurological Diseases, Including Alzheimer's Disease (AD), Secondary Effects of Traumatic Brain Injury (TBI), Amyotrophic Lateral Sclerosis …

An Explainable Deep Learning Prediction Model For Severity Of Alzheimer's Disease From Brain Images, Godwin O. Ekuma

MSU Graduate Theses

Deep Convolutional Neural Networks (CNNs) have become the go-to method for medical imaging classification on various imaging modalities for binary and multiclass problems. Deep CNNs extract spatial features from image data hierarchically, with deeper layers learning more relevant features for the classification application. The effectiveness of deep learning models are hampered by limited data sets, skewed class distributions, and the undesirable "black box" of neural networks, which decreases their understandability and usability in precision medicine applications. This thesis addresses the challenge of building an explainable deep learning model for a clinical application: predicting the severity of Alzheimer's disease (AD). AD …

Tau Kinetics In Alzheimer's Disease, Daniel B. Hier, Sima Azizi, Matthew S. Thimgan, Donald C. Wunsch

Chemistry Faculty Research & Creative Works

The Cytoskeletal Protein Tau is Implicated in the Pathogenesis of Alzheimer's Disease Which is Characterized by Intra-Neuronal Neurofibrillary Tangles Containing Abnormally Phosphorylated Insoluble Tau. Levels of Soluble Tau Are Elevated in the Brain, the CSF, and the Plasma of Patients with Alzheimer's Disease. to Better Understand the Causes of These Elevated Levels of Tau, We Propose a Three-Compartment Kinetic Model (Brain, CSF, and Plasma). the Model Assumes that the Synthesis of Tau Follows Zero-Order Kinetics (Uncorrelated with Compartmental Tau Levels) and that the Release, Absorption, and Clearance of Tau is Governed by First-Order Kinetics (Linearly Related to Compartmental Tau Levels). …

Advanced Glycation End Products In Health And Disease, V. Prakash Reddy, Puspa Aryal, Emmanuel K. Darkwah

Chemistry Faculty Research & Creative Works

Advanced glycation end products (AGEs), formed through the nonenzymatic reaction of reducing sugars with the side-chain amino groups of lysine or arginine of proteins, followed by further glycoxidation reactions under oxidative stress conditions, are involved in the onset and exacerbation of a variety of diseases, including diabetes, atherosclerosis, and Alzheimer's disease (AD) as well as in the secondary stages of traumatic brain injury (TBI). AGEs, in the form of intra- and interprotein crosslinks, deactivate various enzymes, exacerbating disease progression. The interactions of AGEs with the receptors for the AGEs (RAGE) also result in further downstream inflammatory cascade events. The overexpression …

Amyloid Fibril Formation And Polymorphism : A Critical Role Of Sulfur-Containing Amino Acid Residues, Tatiana Quiñones-Ruiz

Legacy Theses & Dissertations (2009 - 2024)

Protein aggregation that results in the formation of amyloid fibrils has been linked to many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The sulfur atoms in methionine (Met) and cysteine (Cys) residues of proteins can be readily oxidized, significantly affecting their properties. Oxidation of sulfur-containing amino acids has recently been shown to affect protein fibrillation. This work presents novel findings on Cys and Met redox reactions that are related to the formation of amyloid fibrils and on the polymorphism of a model fibrillogenic protein, hen egg white lysozyme (HEWL). Biophysical techniques including Raman spectroscopy, atomic force microscopy, electron paramagnetic …

Multi-Method Investigation Of Factors Influencing Amyloid Onset And Impairment In Three Cohorts, Tobey J. Betthauser, Murat Bilgel, Rebecca L. Koscik, Bruno Jedynak, Yang An, Kristina A. Kellett, Abhay Moghekar, Erin M. Jonaitis, Charles K. Stone, Multiple Additional Authors

Mathematics and Statistics Faculty Publications and Presentations

Alzheimer’s disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modelling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer’s disease continuum.

Data were acquired from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of …

Aberrant Crosstalk Between Insulin Signaling And Mtor In Young Down Syndrome Individuals Revealed By Neuronal-Derived Extracellular Vesicles, Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone

Chemistry Faculty Publications

INTRODUCTION: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing.

METHODS: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways.

RESULTS: nEVs isolated from DS children were characterized by a significant increase in pIRS1^Ser636, a marker of …

Deep Learning For Multiclass Classification, Predictive Modeling And Segmentation Of Disease Prone Regions In Alzheimer’S Disease, Maryamossadat Aghili

FIU Electronic Theses and Dissertations

One of the challenges facing accurate diagnosis and prognosis of Alzheimer’s Disease (AD) is identifying the subtle changes that define the early onset of the disease. This dissertation investigates three of the main challenges confronted when such subtle changes are to be identified in the most meaningful way. These are (1) the missing data challenge, (2) longitudinal modeling of disease progression, and (3) the segmentation and volumetric calculation of disease-prone brain areas in medical images. The scarcity of sufficient data compounded by the missing data challenge in many longitudinal samples exacerbates the problem as we seek statistical meaningfulness in multiclass …

From Reaction Kinetics To Dementia: A Simple Dimer Model Of Alzheimer’S Disease Etiology, Michael R. Lindstrom, Manuel B. Chavez, Elijah A. Gross-Sable, Eric Y. Hayden, David B. Teplow

School of Mathematical and Statistical Sciences Faculty Publications and Presentations

Oligomers of the amyloid β-protein (Aβ) have been implicated in the pathogenesis of Alzheimer’s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomerdimer-trimer kinetics to develop a simple mathematical model …

A Continuous-Time Mathematical Model And Discrete Approximations For The Aggregation Of Β-Amyloid, A. S. Ackleh, Saber Elaydi, G. Livadiotis, A. Veprauskas

Mathematics Faculty Research

Alzheimer's disease is a degenerative disorder characterized by the loss of synapses and neurons from the brain, as well as the accumulation of amyloid-based neuritic plaques. While it remains a matter of contention whether β-amyloid causes the neurodegeneration, β-amyloid aggregation is associated with the disease progression. Therefore, gaining a clearer understanding of this aggregation may help to better understand the disease. We develop a continuous-time model for β-amyloid aggregation using concepts from chemical kinetics and population dynamics. We show the model conserves mass and establish conditions for the existence and stability of equilibria. We also develop two …

A New Electrochemical Impedance Biosensor Based On Aromatic Thiol For Alpha-1 Antitrypsin Determination, Hülya Yağar, Hakki Mevlüt Özcan, Osman Mehmet

Turkish Journal of Chemistry

Alpha-1 antitrypsin (A1AT) is one of the acute phase proteins which are synthesized in the liver. A1AT inhibits the activity of many proteases, but its main task is to protect the lungs from the attack of neutrophil elastase. In an autosomal hereditary disease known as alpha-1 antitrypsin deficiency, the A1AT level in blood serum decreases, increasing the risk of developing emphysema, liver apoptosis, and liver cancer. Thus, the detection of A1AT concentration in blood serum is very important. In this study, an impedimetric biosensor was developed, forming an SAM (self-assembled monolayer) with 4-mercaptophenylacetic acid (4MPA) on the surface of the …

Integrated 3d-Qsar, Molecular Docking, And Molecular Dynamics Simulation Studies On 1,2,3-Triazole Based Derivatives For Designing New Acetylcholinesterase Inhibitors, Khalil El Khatabi, Ilham Aanouz, Reda El-Mernissi, Atul Kumar Singh, Mohammed Aziz Ajana, Tahar Lakhlifi, Shashank Kumar, Mohammed Bouachrine

Turkish Journal of Chemistry

Alzheimer's disease (AD) is a multifactorial and polygenic disease. It is the most prevalent reason for dementia in the aging population. A dataset of twenty-six 1,2,3-triazole-based derivatives previously synthetized and evaluated for acetylcholinesterase inhibitory activity were subjected to the three-dimensional quantitative structure-activity relationship (3D-QSAR) study. Good predictability was achieved for comparative molecular field analysis (CoMFA) (Q2 = 0.604, R2 = 0.863, rext2 = 0.701) and comparative molecular similarity indices analysis (CoMSIA) (Q2 = 0.606, R2 = 0.854, rext2 = 0.647). The molecular features characteristics provided by the 3D-QSAR contour plots were quite useful for designing and improving the activity of …

Structure Of Unmodified And Pyroglutamylated Amyloid Beta Peptide In Lipid Membranes, Rowan Hassan

Honors Undergraduate Theses

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that is characterized by brain atrophy, neuronal and synaptic loss, cognitive decline, trouble handling activities of daily life, and ultimately leads to death. Worldwide, at least 30 million people suffer from AD, with 5.8 million suffering in the US alone. Despite extensive basic and clinical research, the underlying molecular mechanisms behind AD remain largely unknown. There are four FDA-approved compounds are used for alleviating symptoms but have no curative potency. The first potentially disease-modifying AD drug, aducanumb, was approved by FDA in June 2021. The main histopathological traits of AD are the …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Combined Ligand And Structure-Based Virtual Screening Approaches For Identification Of Novel Ache Inhibitors, Kader Şahi̇n, Serdar Durdaği

Turkish Journal of Chemistry

The excessive activity of acetylcholinesterase enzyme (AChE) causes different neuronal problems, especially dementia and neuronal cell deaths. Food and Drug Administration (FDA) approved drugs donepezil, rivastigmine, tacrine and galantamine are AChE inhibitors and in the treatment of Alzheimer's disease (AD) these drugs are currently prescribed. However, these inhibitors have various adverse side effects. Therefore, there is a great need for the novel selective AChE inhibitors with fewer adverse side effects for the effective treatment. In this study, combined ligand-based and structure-based virtual screening approaches were used to identify new hit compounds from small molecules library of National Cancer Institute (NCI) …

Personalized Computer-Aided Diagnosis For Mild Cognitive Impairment In Alzheimer's Disease Based On Smri And C Pib-Pet Analysis, Fatma El Zahraa A. El-Gamal, Mohammed M. Elmogy, Ashraf Khalil, Mohammed Ghazal, Jawad Yousaf, Xiaolu Qiu, Hassan H. Soliman, Ahmed Atwan, Hermann B. Frieboes, Gregory Neal Barnes, Ayman S. El-Baz

All Works

© 2013 IEEE. Alzheimer's disease (AD) is a neurodegenerative condition that affects the central nervous system and represents 60% to 70% of all dementia cases. Due to an increased aging population, the number of patients diagnosed with AD is expected to exceed 131 million worldwide by 2050. The disease is characterized by various clinical symptoms and pathological features that define three main sequential decline stages, namely, early/mild, intermediate/moderate and late/severe stages. Although it is considered irreversible, early diagnosis of AD is highly desirable to help preserve cognitive function. However, early diagnosis is difficult due to different factors, including the patient-specific …

Consequences Of Non-Physiological Ligands Binding To Dream On Its Secondary And Tertiary Structures And Interactions With Intracellular Partners., Samiol Azam

FIU Electronic Theses and Dissertations

Downstream regulatory antagonist modulator (DREAM) is 29 kDa neuronal calcium sensor (NCS) protein which is expressed in the hippocampus of the brain. DREAM is a multifunctional protein which is involved in a wide spectrum of biological processes, including regulation of potassium current in brain, modulation of pain, presenilin-1 processing, regulation of memory and learning. Exposure to toxic metals such as Pb2+ and Cd2+ have been associated with different types of neurodegenerative diseases. However, how these toxic metals induce neurotoxicity remains an active area of research. In this study, utilizing a combination of spectroscopic and calorimetric techniques, we demonstrated binding of …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Biomedical Engineering ETDs

Small, biologically active molecules with unique properties and applications are potential solutions to a wide range of threats to global health including infectious agents and neurodegenerative disease. Experimental studies on a class of oligomeric p-phenylene ethynylenes (OPEs) have shown potential both as bioactive antimicrobials and fluorescent sensing agents for tracking amyloid-β (Aβ) aggregates found in Alzheimer’s Disease (AD). A second type of small molecule with potential applications in AD therapy, curcumin, has been found to interfere with Aβ fibril growth. Curcumin also attenuates Aβ-membrane interactions and Aβ toxicity. Our goal has been to use computational techniques to better understand the …

The Transformative Possibilities Of The Microbiota And Mycobiota For Health, Disease, Aging, And Technological Innovation, Lucas Jones, Jessica Kumar, Adil Mistry, Thriveen Sankar Chittoor Mana, George Perry, Prakash Reddy, Mark Obrenovich

Chemistry Faculty Research & Creative Works

The gut microbiota is extremely important for the health of the host across its lifespan. Recent studies have elucidated connections between the gut microbiota and neurological disease and disorders such as depression, anxiety, Alzheimer's disease (AD), autism, and a host of other brain illnesses. Dysbiosis of the normal gut flora can have negative consequences for humans, especially throughout key periods during our lifespan as the gut microbes change with age in both phenotype and number of bacterial species. Neurologic diseases, mental disorders, and euthymic states are influenced by alterations in the metabolites produced by gut microbial milieu. We introduce a …

Evaluating Trajectories Of Episodic Memory In Normal Cognition And Mild Cognitive Impairment: Results From Adni, Xiuhua Ding, Richard J. Charnigo, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Alzheimer’S Disease Neuroimaging Initiative

Statistics Faculty Publications

BACKGROUND: Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.

METHOD: To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.

RESULTS: There were …

The Use Of Tissue And Serum ”˜Omics' Methods To Characterize Disease, Ying Ding

Theses and Dissertations

Preeclampsia (PE) is a multisystem disorder that contributes to maternal and fetal mortality and morbidity worldwide. It is characterized by de-novo hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Evidence suggested that endogenous digitalis-like factor (EDLF) contributes to the pathogenesis of PE, and that the potential source of EDLF is the placenta. EDLF can inhibit the sodium pump (SP) specifically and may lead to hypertension, it has also been associated with hypoxia, oxidative stress and other abnormalitites present in PE.We studied whether normal human placenta responded to SP inhibition casued by EDLF with a change …

Design And Assessment Of Small Molecules As Free Radical Scavengers And Potential Multi-Target Therapeutic Agents Against Alzheimer’S Disease, Diabetes And Cancer, William Horton

Graduate Doctoral Dissertations

Complex diseases such as Alzheimer’s disease (AD), diabetes and cancer are difficult to manage with single target treatment approaches and unfortunately, they are wide-spread. For example, over 16 million people are expected to have AD in the US by 2050, thus new therapeutic approaches have to be developed. Multi-functional drug candidates have gained increasing popularity in treating complex diseases. The impact of oxidative stress in almost every disease progression makes them essential components in therapies for complex diseases. Endogenous systems typically maintain redox homeostasis within the cell, but in the diseased state these systems fail to alleviate oxidative stress. Supplementation …

A Discrete Mathematical Model For The Aggregation Of Β-Amyloid, Maher A. Dayeh, George Livadiotis, Saber Elaydi

Mathematics Faculty Research

Dementia associated with the Alzheimer's disease is thought to be correlated with the conversion of the β − Amyloid (Aβ) peptides from soluble monomers to aggregated oligomers and insoluble fibrils. We present a discrete-time mathematical model for the aggregation of Aβ monomers into oligomers using concepts from chemical kinetics and population dynamics. Conditions for the stability and instability of the equilibria of the model are established. A formula for the number of monomers that is required for producing oligomers is also given. This may provide compound designers a mechanism to inhibit the Aβ aggregation.

Treatment Of Mci And Alzheimer's Disease, Mark A. Lovell, Bert C. Lynn

Chemistry Faculty Patents

The present invention provides, among other things, therapeutic compositions and methods that can effectively treat, slow or prevent a neurological disease (e.g., a neurodegenerative disease, e.g., mild cognitive impairment (MCI) or Alzheimer's disease (AD)), in particular, based on therapeutically effective amount of nifedipine, oxidized or nitroso nifedipine derivatives, lactam (e.g., a compound of formula (Ic) or (Ic-i), e.g., NFD-L1), thyroxine (T4), triiodothyronine (T3) and combinations thereof.

Improving The Detection Limit Of Tau Aggregates For Use With Biological Samples, Emily Rickman Hager

Electronic Theses and Dissertations

The protein Tau is found in neurofibrillary tangles in Alzheimer's disease and over 20 other neurodegenerative diseases. An assay has been developed to detect minute amounts of fibrils from human brain tissue. This assay subjects brain tissue extract and recombinant Tau to several rounds of sonication and incubation. Incubation allows recombinant Tau to add itself to the ends of the existing fibrils in brain tissue extract. Sonication breaks the existing fibrils in the brain tissue extract offering more ends for Tau to add onto. Cycles of sonication and incubation have been shown to allow for amplification of Tau fibrils from …

Process For Detection Of Alzheimer's Disease From A Serum Sample, Mark A. Lovell, Bert C. Lynn

Chemistry Faculty Patents

Disclosed is a method of detecting a concentration of a biomarker in a human subject having or being at risk of developing Alzheimer's disease or Mild Cognitive Impairment (MCI). Also disclosed is a process for detecting a concentration of a biomarker in a human subject having or being at risk of developing Alzheimer's disease or Mild Cognitive Impairment (MCI) comprising (a) detecting a first concentration of lipocalin-PDS/TTR complex in a blood sample or urine sample from the subject, (b) determining a second concentration of PDS/TTR complex in a blood sample or urine sample from an unaffected individual, and ( c) …