Classical AD Research Articles

NONLINEAR RELATIONSHIP BETWEEN BETA-AMYLOID (1-42) AND TOTAL-TAU: DO THEY DEFINE PROGRESSION?

Biomarkers offer the potential for an unbiased, objective picture of underlying disease pathology. Classical AD biomarkers such as cerebrospinal fluid (CSF) beta-amyloid (Aβ1–42) and total-tau (t-tau) are considered suitable endpoints in clinical trials of preventative treatments, providing a clear picture of the development of AD pathology in the clinically silent stage (pre-clinical) of the disease. We performed a correlation analysis on a selection of biochemical (CSF Aβ1–42, and CSF t-tau), neurophysiological (FDG-PET), volumetric (hippocampal volume), and cognitive markers, using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, at baseline and longitudinally. We describe 4 biological (biochemical) phenotypes (CSF Aβ1–42 >= 192 pg/mL and CSF t-tau <= 93 pg/mL as normal) at baseline, and compare these with clinically derived diagnostic groupings. Per capita rate of changes in CSF Aβ and t-tau are quantified, and population estimates, in addition to individual trajectories, are assessed in relation to their biological phenotype and change in cognitive diagnosis. A strong, inverse correlation was found between CSF Aβ1–42 and CSF t-tau (r = -0.43), as well as CSF Aβ1–42 and ADAScog-11 (r = -0.38). A ‘phase’ plot of the concentrations of Aβ1–42 and t-tau, show a highly non-linear “right angle” relationship. We observe strong but imperfect concordance between biological phenotypes and cognitive diagnosis, 63% of AD-diagnoses individuals present with an ‘AD typical’ biological phenotype while 49.8% of cognitively normal (CN) individuals present with a ‘CN typical’ phenotype at baseline. A small per capita annual rate of change is observed in CSF Aβ1–42 and CSF t-tau concentrations relative to variance. The greatest per capita rate of change in Aβ occurs in CN individuals who do not progress to MCI/AD across follow-up (CN-NP), mean rate of -2.4 pg/mL/year, and those with progressive MCI (MCI-P) accumulate the largest amount of t-tau, mean rate of 2.2 pg/mL/year. Our findings support the ordering of biomarker changes suggested by the amyloid cascade hypothesis. The high variance in CSF Aβ and t-tau concentrations, within subjects longitudinally, impairs quantification and visualisation of individual biomarker trajectories. The phase plots of Aβ1–42 versus t-tau suggest a highly non-linear dynamic between the two variables.

CFD and Experimental Studies on Wind Turbines in Complex Terrain by Improved Actuator Disk Method

In this paper, an onshore wind farm in mountainous area of southwest China was investigated through numerical and experimental methods. An improved actuator disk method, taking rotor data (i.e. blade geometry information, attack angle, blade pitch angle) into account, was carried out to investigate the flow characteristic of the wind farm, especially the wake developing behind the wind turbines. Comparing to the classic AD method and the situ measurements, the improved AD shows better agreements with the measurements. The turbine power was automatically predicted in CFD by blade element method, which agreed well with the measurement results. The study proved that the steady CFD simulation with improved actuator disk method was able to evaluate wind resource well and give good balance between computing efficiency and accuracy, in contrary to much more expensive computation methods such as actuator-line/actuator-surface transient model, or less accurate methods such as linear velocity reduction wake model.

Alterations in the Balance of Amyloid-β Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer's Disease Patients.

We recently demonstrated that soluble forms of the amyloid-β protein precursor (sAβPP) assemble into multimeric complexes in cerebrospinal fluid (CSF), which contributes to the underestimation of specific sAβPP species when assessed by ELISA. To circumvent this issue, we analyzed by SDS-PAGE large fragments of sAβPP and their variants in the CSF from Alzheimer's disease (AD; n = 20) and control (n = 20) subjects, probing with specific antibodies against particular domains. Similar levels of sAβPPα and sAβPPβ protein were found in CSF samples from AD and controls, yet there appeared to be a shift in the balance of the soluble full-length AβPP (sAβPPf) species in AD samples, with a decrease in the proportion of the lower (∼100 kDa) band relative to the upper (∼120 kDa) band. Similar differences were observed in the contribution of the major KPI-immunoreactive AβPP species. CSF samples also displayed differences in the correlations of AβPP species with classical AD biomarkers, particularly with respect to the Aβ42 peptide. The differences reveal alterations that probably reflect pathophysiological changes in the brain.

Path diversified multi-QoS optimization in multi-channel wireless mesh networks

Wireless mesh networks (WMNs) have become a promising solution for quick and low-cost spreading of Internet accesses and other network services. Given the mesh topology, multiple paths are often available between node pairs, which thus naturally endorse path-diversified transmission. Unfortunately, like in wired networks, discovering completely disjoint paths in a WMN remains an intractable problem. It indeed becomes more challenging given the interferences across wireless channels in a WMN, not to mention that applications may demand heterogeneous QoS optimizations across different paths. The availability of multiple channels in advanced WMNs however sheds new lights into this problem. In this paper, we show that, as long as the best channels with different QoS metrics are not overlapped between neighboring node pairs, complete disjoint paths with heterogeneous QoS targets are available in a multi-channel WMN. We present efficient solutions to discover such paths, particularly for bandwidth- and delay-optimization. We also develop novel algorithms for accurately estimating path bandwidth and delay in the multi-channel environment. These lead to the design of a practical protocol that extends the classical Ad hoc On-demand Multi-path Distance Vector (AOMDV). Through extensive simulations, we show that our protocol yields significant improvement over state-of-the-art multi-path protocols in terms of both end-to-end throughput and delay.

The Autosomal Dominant Facioscapuloperoneal Muscular Dystrophy with 4q35 Chromosomal Deletion in Two Russian Families

We give the description of the pattern of muscle affections in two autosomal dominant 4q35-linked facioscapuloperoneal muscular dystrophy (FSPMD) families in which the patients were re-examined by V.K. in 24 - 28 and 35 - 37 years after their first examination. The disease started with initial involvement of facial and shoulder girdle muscles and in some time later of the peroneal group (anterior tibial) of muscles became involved. However, in two probands the dystrophic process gradually extended to the thighs (posterior group of muscles, namely), pelvic girdle (gluteus maximus muscles, namely) and the upper arm (biceps brachii muscles were slightly affected) and in three their relatives with clinical facioscapuloperoneal (FSP) phenotype the severe involvement of some posterior thigh muscles during MRI study was revealed. In this connection, the term “facioscapulolimb muscular dystrophy, type 2 (FSLD2), a descending type with a “jump” with initial FSP phenotype” would be more correct instead of the name facioscapuloperoneal muscular dystrophy. The FSP phenotype constitutes merely a stage in the development of FSLD2. The CT and MRI pattern of muscle involvement does not fully correlate with clinical pattern of muscle affection. We suppose that classical AD FSPMD is an independent clinical form which is different from the classical FSHD although both of them are connected with 4q35 chromosomal deletion.

Acute Aortic Intramural Hematoma

Acute aortic intramural hematoma (IMH) is an important subgroup of aortic dissection, and controversy surrounds appropriate management. Patients with acute aortic syndromes in the International Registry of Acute Aortic Dissection (1996-2011) were evaluated to examine differences between patients (based on the initial imaging test) with IMH or classic dissection (AD). Of 2830 patients, 178 had IMH (64 type A [42%], 90 type B [58%], and 24 arch). Patients with IMH were older and presented with similar symptoms, such as severe pain. Patients with type A IMH were less likely to present with aortic regurgitation or pulse deficits and were more likely to have periaortic hematoma and pericardial effusion. Although type A IMH and AD were managed medically infrequently, type B IMH were more frequently treated medically. Overall in-hospital mortality was not statistically different for type A IMH compared to AD (26.6% versus 26.5%; P=0.998); type A IMH managed medically had significant mortality (40.0%), although less than classic AD (61.8%; P=0.195). Patients with type B IMH had a hospital mortality that was less but did not differ significantly (4.4% versus 11.1%; P=0.062) from classic AD. One-year mortality was not significantly different between AD and IMH. Acute IMH has similar presentation to classic AD but is more frequently complicated with pericardial effusions and periaortic hematoma. Patients with IMH have a mortality that does not differ statistically from those with classic AD. A small subgroup of type A IMH patients are managed medically and have a significant in-hospital mortality.

Mixed Vector Immunization With Recombinant Adenovirus and MVA Can Improve Vaccine Efficacy While Decreasing Antivector Immunity

Substantial protection can be provided against the pre-erythrocytic stages of malaria by vaccination first with an adenoviral and then with an modified vaccinia virus Ankara (MVA) poxviral vector encoding the same ME.TRAP transgene. We investigated whether the two vaccine components adenovirus (Ad) and MVA could be coinjected as a mixture to enhance protection against malaria. A single-shot mixture at specific ratios of Ad and MVA (Ad+MVA) enhanced CD8+ T cell-dependant protection of mice against challenge with Plasmodium berghei. Moreover, the degree of protection could be enhanced after homologous boosting with the same Ad+MVA mixture to levels comparable with classic heterologous Ad prime-MVA boost regimes. The mixture increased transgene-specific responses while decreasing the CD8+ T cell antivector immunity compared to each vector used alone, particularly against the MVA backbone. Mixed vector immunization led to increased early circulating interferon-γ (IFN-γ) response levels and altered transcriptional microarray profiles. Furthermore, we found that sequential immunizations with the Ad+MVA mixture led to consistent boosting of the transgene-specific CD8+ response for up to three mixture immunizations, whereas each vector used alone elicited progressively lower responses. Our findings offer the possibility of simplifying the deployment of viral vectors as a single mixture product rather than in heterologous prime-boost regimens.

Rapidly Progressive Alzheimer's Disease: A Multicenter Update

The objective was to characterize a rapidly progressive subtype of Alzheimer's disease (rpAD). Multicenter (France, Germany, Japan, Spain) retrospective analyses of neuropathologically confirmed rpAD cases initially classified as prion disease due to their clinical phenotype were performed. Genetic properties, cerebrospinal fluid biomarkers, neuropathology, and clinical features were examined. Eighty-nine patients were included (median survival 10 months). APOE and PRNP codon 129 genotype distribution paralleled a healthy control group. APOE ε4 homozygosity was absent. Cerebrospinal fluid biomarkers were abnormal, but within a range as expected for classic AD, except for proteins 14-3-3, which were detectable in 42%. Thus, evidence of the existence of rpAD is accumulating. The APOE profile is intriguing, suggesting that this very rapid disease form might represent a distinct subtype of Alzheimer's disease.

Abstract 17170: Acute Aortic Intramural Hematoma: an Analysis from the International Registry of Acute Aortic Dissection

Background: Acute aortic intramural hematoma (IMH) represents an important subgroup of aortic dissection though controversy continues to surround the appropriate management. Methods: We evaluated patients with acute aortic syndromes in the IRAD registry (between 1996 and 2011) and examined differences between patients (based on the initial imaging test) with IMH or classic dissection (AD). Results: Of 2908 patients, 182 had IMH (72 type A (TA), 39.6%, 110 type B (TB), 60.4%). Patients with IMH were older in both TA (68.9 years vs. 61.4, p&lt;0.001) and TB (69.3 vs 62.7, p&lt;0.001), and more frequently female in TA (44.4% vs 32.3%, p=.031). Patients presented with similar symptoms such as severe pain in TA (98.4% vs 91.6%, p=NS) and TB (95.7% vs 93.0%, p=NS). Patients with TA IMH were less likely to present with aortic regurgitation (37.3% vs 54.8%, p=.008) or pulse deficits (16.7% vs31.5%, p=.015). Patients with TA IMH were more likely to have periaortic hematoma (47.5% vs 19.9%, p&lt;0.001) and pericardial effusion (60.0% vs 41.2%, p=.002). Patients with IMH were more likely than classic AD to be managed medically (TA, 22.2% vs 12.6%, p=.017, type B 85.5% vs 62.9%, p&lt;0.001). Overall in-hospital mortality was similar for type A IMH (26.4% vs 26.4%, p=NS); those with type A IMH managed medically had significant mortality (37.5%) though less than those with classic AD (58.5%, p=NS). Those with type B IMH had lower in hospital mortality (4.5% vs 10.9%, p=.043) than classic AD. One year mortality was similar for both groups. Conclusion: The IRAD registry includes 182 cases of IMH and represents the largest series to date on this important variant of AD. Acute IMH has similar presentation to classic AD but is more frequently complicated with pericardial effusions and periaortic hematoma. Patients with IMH have similar mortality to those with classic AD. Although a substantial subgroup of type A patients with IMH are managed medically, they do have a significant hospital mortality.

Review of AdS/CFT Integrability, Chapter II.1: Classical AdS 5 × S 5 String Solutions

We review basic examples of classical string solutions in AdS 5 × S 5. We concentrate on simplest rigid closed string solutions of circular or folded type described by integrable 1-d Neumann system but mention also various generalizations and related open-string solutions.

Halogenophilic and classical Ad N E mechanisms in nucleophilic vinylic substitution reactions involving the anions of transition metal carbonyls

The mechanism of the reaction of carbonylate anions ([M(CO) n L]–) with highly activated vinyl halides (Hal = Cl, Br, I) was investigated by the method of “anion traps” – the effect of proton donors on the composition of the reaction products. It was demonstrated that the reactions with PhCHal=C(Z)2 (Hal = Br, I;Z=CN, CO2Et) and PhCN=CClI take place through initial attack by the carbonylate at the halogen atom, the reactions with PhCCl=C(CO2Et)2 and PhCOCH=CHHal (Hal = Cl, I) take place through attack by the carbonylate at the π bond (AdNE mechanism), and in the case of E-and Z-PhCN=CHI the two mechanisms operate concurrently. The main laws determining the reaction mechanisms are analyzed.

Microtubule destabilization leads to APP phosphorylation and processing: Implications for Alzheimer's disease pathogenesis

However, also prion proteins produced by neurons, can form amyloid plaques in the brain. In variant Creutzfeldt Jakob disease (vCJD), sporadic CJD forms with a longer duration, hereditary CJD and Gerstmann Straussler Scheinker’s disease (GSS) prion amyloid plaques can be found. In the present immunohistochemical study we investigated the presence of amyloid associated proteins such as complement and alpha1-antichymotrypsin (ACT), microglia (HLADR), ubiquitin and tau in 4 different forms of prion diseases with prion amyloid plaques with or without prion cerebral amyloid angiopathy (CAA) and compared the results with the findings in classical AD. Methods: Cortical tissue obtained at autopsy was used from 3 vCJD (16, 37 and 49 y old), 2 sporadic CJD patients with longer duration (MM2, VV2 forms; resp. 55 y and 58 y) and 3 different GSS patients (57y, 57y, 45y) including 2 novel prion mutations, i.e. Y226X and Q227X stop codon mutations, and 5 AD cases (29y 76y). Immunohistochemistry was performed on formalin fixed tissue using antibodies against Abeta 1-17, prion proteins (3F4), complement C3b, HLADR, ubiquitin and Tau (AT8) and some sections were counterstained with Congo red. Cryostat sections were used for staining with antibodies against complement C3c and ACT. Results: Complement proteins were found in amyloid deposits both in AD and in prion diseases without Abeta. In a case with extensive prion CAA, complement was also detected in the amyloidotic vessel wall. Clustering of microglia was seen both in AD plaques and around prion plaques but also around prion CAA. Extensive neurofibrillary degeneration with numerous tangles throughout the cortex was found in the stopcodon Q227X patient (aged 45y) mimicking the AD cases. In the MM2 prion case (55 y) tau and ubiquitin was found especially near prion plaques. Prion CAA showed a mild tau and ubiquitin positivity around the vessel walls. No tau was found in the vCJD cases. Conclusions: Inflammatory changes and neurofibrillary degeneration seems to be related to cerebral amyloidosis irrespective the type of amyloid.

SOLITONS AND ADS STRING SOLUTIONS

In this contribution we describe some soliton based techniques for generating classical AdS string solutions. The methods introduced are useful for further understanding of rotating AdS configurations with spikes which correspond to higher twist operators in SYM theory. The main identification (accomplished in arXiv:0712.1193) between solitons and string spikes is reviewed and extended. We desribe how inverse scattering technique can be applied for reconstructing AdS string configurations from soliton solutions of sinh-Gordon theory (in the example of AdS3).

Wide‐Band Spectroscopy of Two Radio Bursts on AD Leonis

We report high-time-resolution, broadband spectroscopic observations of two radio bursts on the classical flare star AD Leonis. The observations were acquired by the 305 m telescope at Arecibo Observatory on 2003 June 13-14. Using the Wideband Arecibo Pulsar Processor, these observations sampled a total bandwidth of 400 MHz, distributed over a 500 MHz frequency range, 1120--1620 MHz, with a frequency resolution of 0.78 MHz and a time resolution of 10 ms. A radio burst observed on June 13 is characterized by the presence of multitudes of short duration ($\Delta t \sim$30 ms), high brightness temperature ($T_{b}>10^{14}$K), highly circularly polarized, fast-drift radio sub-bursts, with median bandwidths $\Delta \nu/\nu \sim$5%. The inverse drift rates are small, and have a symmetric distribution (both positive and negative frequency drifts) with a Gaussian FWHM inverse drift rate of 4.5$\times10^{-4}$ s/MHz. The fast-drift sub-bursts occur at a mean rate of 13 s$^{-1}$ and show no evidence for periodic recurrence. The fast-drift radio events on AD Leo are highly reminiscent of solar decimetric spike bursts. We suggest the emission is due to fundamental plasma radiation. A second highly circularly polarized radio burst, recorded June 14, has markedly different properties: a smoothly varying intensity profile characterized by a slow drift in frequency with time (-52 MHz s$^{-1}$). Under the assumption that the source is due to a disturbance propagating through the low corona, a source size of 0.1--1 R$_{\star}$ is inferred, implying a brightness temperature range 6$\times10^{11}$--6$\times10^{13}$K: another example of a coherent radio burst.

Large spin limit of AdS5× S5 string theory and low energy expansion of ferromagnetic spin chains

By considering AdS 5× S 5 string states with large S 5 angular momenta one can provide non-trivial quantitative checks of the AdS/CFT duality. A string rotating in S 5 with two angular momenta J 1, J 2 is dual to an operator in N=4 SYM theory whose conformal dimension can be computed by diagonalizing a (generalization of) spin 1/2 Heisenberg chain Hamiltonian. It was recently argued and verified to lowest order in a large J= J 1+ J 2 expansion, that the Heisenberg chain can be described using a non-relativistic low energy effective 2d action for a unit vector field n i which exactly matches the corresponding large J limit of the classical AdS 5× S 5 string action. In this paper we show that this agreement extends to the next order and develop a systematic procedure for computing higher orders in such large angular momentum expansion. This involves several non-trivial steps. On the string side, we need to choose a special gauge with a non-diagonal world-sheet metric which insures that the angular momentum is uniformly distributed along the string, as indeed is the case on the spin chain side. We need also to implement an order by order redefinition of the field n i to get an action linear in the time derivative. On the spin chain side, it turns out to be crucial to include the effects of integrating out short wave-length modes. In this way we gain a better understanding of how (a subsector of) the string sigma model emerges from the dual gauge theory, allowing us to demonstrate the duality beyond comparing particular examples of states with large J.

Changes of Aortic Morphology after Aortic Dissection Evaluated by CT Angiography

Background and Objectives:In aortic dissection (AD, CT angiography (CTA is useful both in initial dia- gnosis and long term follow-up. In this study, we used CTA to evaluate the morphologic changes of aorta after AD. Subjects and Methods:We reviewed the initial and follow-up CTA images of 43 patients with AD. The diagnoses were double-lumen dissection (n=13, intramural hematoma (n=11, and residual dissection after surgery (n=19. The duration of CTA follow-up was 3.3±1.9 years (range 7-89 months. After reviewing the CTA images of the thoracic aorta level, and of the upper and lower abdominal aorta levels, we compared the areas of total lumen, true lumen and false lumen and the area ratio of true/total lumen. Results:Changes in luminal areas were greatest in the thoracic aorta, where both the true lumen area and the ratio of true/total lumen area increased. Subgroup analysis revealed that although the total lumen area increased significantly in the classic AD group, no changes were noted in the ratio of true/total lumen area. Only the increase in false lu- men area (from 5.8 cm 2 to 9.0 cm 2 was significant (p=0.036. In patients with intramural hematoma, a decr- ease in total lumen area and an increase in the ratio of true/total lumen area were noted. Conclusion:In classic AD, false lumen dilatation occurs with false lumen enlargement, whereas in intramural hematoma total aorta size decreases with any increase in the ratio of true/total lumen area. ( ( ( (Korean Circulation J 2002;32(1 :53-60

Brain aging and Alzheimer's disease; use it or lose it

(1) Alzheimer's disease is a multifactorial disease in which age and APOE-epsilon 4 are important risk factors. (2) The neuropathological hallmarks of AD, i.e. amorphous plaques, neuritic plaques (NPs), pretangles, neurofibrillary tangles (NFT) and cell death are not part of a single pathogenetic cascade but may occur independently. (3) In brain areas where classical AD changes, i.e. NPs and NFTs, are present, such as the CA1 area of the hippocampus, the nucleus basalis of Meynert and the tuberomamillary nucleus, a decreased metabolic rate is found. The decreased metabolic rate appears not to be induced by the presence of pretangles, NFT or NPs. (4) Decreased metabolic rate may precede cognitive impairment and is thus an early occurring hallmark of AD, which, in principle, may be reversible. The observation that the administration of glucose or insulin enhances memory in AD patients also supports the view that AD has a metabolic basis. (5) Moreover, several observations in postmortem brain indicate that activated neurons are better able to withstand aging and AD, a phenomenon paraphrased by us as 'use it or lose it'. (6) It is, therefore, attractive to direct the development of therapeutic strategies towards restimulation of neuronal metabolic rate in order to improve cognition and other symptoms in AD. A number of pharmacological and non-pharmacological studies support the concept that activation of the brain has beneficial effects and may, to a certain degree, restore several aspects of cognition and other central functions. For instance, the circadian system may be restimulated in AD patients by exposing them to more light or transcutaneous nerve stimulation. A procedure has been developed to culture human postmortem brain tissue that allows testing of the efficacy of putative stimulatory compounds such as neurotrophins.

Variant Alzheimer disease with spastic paraparesis: neuropathological phenotype.

Variant Alzheimer disease (varAD) is clinically characterized by the combination of presenile dementia with spastic paraparesis and is caused by certain mutations of the presenilin 1 (PS-1) gene. We now present the unusual neuropathological phenotype of varAD as seen in 5 affected members of the original Finnish family with a genomic deletion encompassing exon 9 of the PS-1 gene. Their primary and association cortices and hippocampus showed a profusion of eosinophilic, roundish structures with distinct borders termed "cotton wool" plaques (CWPs). The CWPs were immunoreactive for Abeta42/43 but weakly or not at all for Abeta40 isoforms of the amyloid beta peptide (Abeta). They were devoid of a congophilic core, and fibrillar amyloid could not be identified within them by electron microscopy. Confocal microscopy showed reduced density of axons within individual CWPs and only few CWP-related PHF-tau-positive dystrophic neurites. CWPs were particularly numerous in the medial motor cortex representing the lower extremities, and degeneration of the lateral corticospinal tracts was observed at the level of the medulla oblongata and the spinal cord. In addition to the predominant CWPs, variable numbers of diffuse and cored plaques were found in the cerebral cortex. Diffuse and non-neuritic cored amyloid plaques but no CWPs occurred in the cerebellum. In conclusion, varAD in this Finnish family is distinct from classic AD because of the degeneration of lateral corticospinal tracts, predominance of CWPs devoid of fibrillar amyloid cores in the cerebral cortex, and presence of non-neuritic amyloid plaques in the cerebellum.

Qp Spaces on Riemann Surfaces

AbstractWe study the function spaces Qp(R) defined on a Riemann surface R, which were earlier introduced in the unit disk of the complex plane. The nesting property Qp(R) ⊆Qq(R) for 0 &lt; p &lt; q &lt; ∞ is shown in case of arbitrary hyperbolic Riemann surfaces. Further, it is proved that the classical Dirichlet space AD(R) ⊆ Qp(R) for any p, 0 &lt; p &lt; ∞, thus sharpening T. Metzger's well-known result AD(R) ⊆ BMOA(R). Also the first author's result AD(R) ⊆ VMOA(R) for a regular Riemann surface R is sharpened by showing that, in fact, AD(R) ⊆ Qp,0(R) for all p, 0 &lt; p &lt; ∞. The relationships between Qp(R) and various generalizations of the Bloch space on R are considered. Finally we show that Qp(R) is a Banach space for 0 &lt; p &lt; ∞.

Dopamine D2 receptor bands in normal human temporal cortex are absent in Alzheimer's disease

A modular organization of bands enriched in high concentrations of D2 receptors are observed throughout the rostral to caudal aspects of the temporal cortex of the normal human at postmortem, but are most frequently observed in the inferior and superior temporal cortices [S. Goldsmith, J.N. Joyce, Dopamine D2 receptors are organized in bands in normal human temporal cortex, Neuroscience 74 (1996) 435–451]. In the tissue derived at postmortem from Alzheimer's disease cases (AD), these D2 receptor-enriched modules were found to be largely absent at rostral and mid-levels of the temporal cortex. Regions exhibiting this loss of receptor binding also showed a marked reduction in the number of pyramidal neurons stained for D2 mRNA. In addition, the AD material exhibited numerous thioflavin-positive plaques and tangle-filled extraneuronal (ghost) pyramidal neurons that were D2 mRNA-negative. Regions that are the earliest affected and most susceptible to classical AD pathology are also most sensitive to the loss of D2 receptors. These results, along with our previous data [J.N. Joyce, C. Kaeger, H. Ryoo, S. Goldsmith, Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease, Neurosci. Lett. 154 (1993) 171–174; H. Ryoo, J.N. Joyce, The loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in Alzheimer's disease, J. Comp. Neurol. 348 (1994) 94–110], indicate that specific pathways enriched with D2 receptors, including that within modules of higher order association cortices of the temporal lobe and continued through segregated pathways within the parahippocampus and hippocampus, are particularly susceptible to the loss in AD. These dopamine D2 receptor-enriched modules may play an important role in the reciprocal activity of large groups of neurons in these high-order association cortical regions. Hence, the loss of the D2 receptor-enriched modules in Alzheimer's disease contributes to disturbances in information processing in these high-order association cortices, and may promote the cognitive and non-cognitive impairments observed in Alzheimer's disease.