GSE5281 Human Brain Best 102 (Jul09) RMA

GSE5281 Human Brain Best 102 (Jul09) RMA
Accession number: GN232

Human brain expression data in patients with Alzheimer's disease and in age-matched elderly normal subjects. This data set is taken from GEO GSE5281. Samples were laser-captured from cortical layer 3 (except the hippocampus) and run on the Affymetrix U133 Plus 2.0 array. We renormalized the data to an average expression of 8 units on a log2 scale. Only then best 102 array data sets were entered into GeneNetwork: those with mean correlations of better than 0.88 with all other arrays. Case IDs have the following code structure: Brain Region, GEO ID, Sex, Age, Disease Status. E119615M63N is a sample of the entorhinal cortex of case GSM119615, a male 63 year old normal case. The tissue codes are E = enorhinal cortex, H = hippocampus pyramidal layer, MT = medial temporal cortex, PC = porterior cingulate cortex, SP = supeior frontal cortex, V = primary visual cortex. GeneNetwork does not allow sophisticated display of the data, but you can perform correlation analyses of any of the 56,000 probe sets. For example expression of the APP transcript is higher in the AD cases and correlates well with many other AD related genes.
Please cite: Liang WS, Dunckley T, Beach TG, Grover A et al. (2007) Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 28:311-22
Summary: (Taken verbatim from the GEO record)

Information about the genes that are preferentially expressed during the course of Alzheimer’s disease (AD) could improve our understanding of the molecular mechanisms involved in the pathogenesis of this common cause of cognitive impairment in older persons, provide new opportunities in the diagnosis, early detection, and tracking of this disorder, and provide novel targets for the discovery of interventions to treat and prevent this disorder. Information about the genes that are preferentially expressed in relationship to normal neurological aging could provide new information about the molecular mechanisms that are involved in normal age-related cognitive decline and a host of age-related neurological disorders, and they could provide novel targets for the discovery of interventions to mitigate some of these deleterious effects.
Aim 1. Collect brain samples from three Alzheimer’s Disease Centers (ADCs) for subsequent gene expression profiling. Individuals will be stratified with respect to diagnostic groups (using both clinical and neuropathological criteria), age groups, and APOE genotype. 150 individual brains will be sampled from the Arizona ADC, the Duke University ADC, and the Washington University ADC. Miniscule sample sizes (200 um of sectioned tissue) from six brain regions that are histopathologically or metabolically relevant to AD and aging will be collected, ensuring that this proposal does not deplete the national resource. Frozen and fixed samples will be sent to Phoenix, sectioned in a standardized fashion, and then returned. Aim 2. Tissue heterogeneity will be eliminated prior to expression profiling by performing laser capture microscopy on all brain regions. Aim 3. Expression profile LCM-captured cells on the Affymetrix U133 Plus 2.0 array (~55,000 transcripts), and quickly provide these data to the community at large. Aim 4. Identify pathogenic cascades related to each of the clinico-pathologic correlates using unsupervised and supervised analyses coupled with a hypothesis-driven approach. Aim 5. Validation of the expression correlates at the protein and functional levels.
Scientific progress in the last few years has improved our understanding of AD and raised the hope of identifying treatments to halt the progression and prevent the onset of this disorder. For instance, researchers have begun to characterize the cascade of molecular events which lead to the major histopathological features of the disorder: neuritic plaques, which contain extra-cellular deposits of amyloid beta-peptides (Abeta); neurofibrillary tangles, which contain the hyperphosphorylated form of the intracellular, microtubule-associated protein, tau; and a loss of neurons and synapses. These molecular events provide targets for the development of promising new treatments. For example, A-beta has been postulated to trigger a cascade of events that are involved in the pathogenesis of AD. This proposal hopes to provide new information about the genes that are preferentially expressed in the development of AD histopathology, including the over-expression of APP, amyloid-induced neurotoxicity, and hyperphosphorylation of tau, as well as bring clarity to the metabolic abnormalities that seem to play a role in dementia and AD development and pathology.
We will perform LCM on 6 brain regions with about 14 biological replicates per brain region. The brain regions are as follows: 1) entorhinal cortex 2) hippocampus 3) medial temporal gyrus 4) posterior cingulate 5) superior frontal gyrus and 6) primary visual cortex. We will collect layer III pyramidal cells from the white matter in each region, isolate total RNA from LCMed cell lysates, and perform double round amplification of each sample for array analysis.

Index	GEO Series	Organ Region	Tissue	Case ID	Age	Sex	Normalization
1	GSM119615	Entorhinal Cortex	Normal	E119615M63N	63	M	Included
2	GSM119616	Entorhinal Cortex	Normal	E119616M85N	85	M	Excluded
3	GSM119617	Entorhinal Cortex	Normal	E119617M80N	80	M	Excluded
4	GSM119618	Entorhinal Cortex	Normal	E119618M80N	80	M	Excluded
5	GSM119619	Entorhinal Cortex	Normal	E119619F102N	102	F	Included
6	GSM119620	Entorhinal Cortex	Normal	E119620M79N	79	M	Excluded
7	GSM119621	Entorhinal Cortex	Normal	E119621M76N	76	M	Excluded
8	GSM119622	Entorhinal Cortex	Normal	E119622M83N	83	M	Excluded
9	GSM119623	Entorhinal Cortex	Normal	E119623M79N	79	M	Excluded
10	GSM119624	Entorhinal Cortex	Normal	E119624F88N	88	F	Excluded
11	GSM119625	Entorhinal Cortex	Normal	E119625F82N	82	F	Excluded
12	GSM119626	Entorhinal Cortex	Normal	E119626M69N	69	M	Excluded
13	GSM119627	Entorhinal Cortex	Normal	E119627M78N	78	M	Excluded
14	GSM238763	Entorhinal Cortex	Alzheimer's	E238763F82A	82	F	Excluded
15	GSM238790	Entorhinal Cortex	Alzheimer's	E238790F86A	86	F	Included
16	GSM238791	Entorhinal Cortex	Alzheimer's	E238791F93A	93	F	Excluded
17	GSM238792	Entorhinal Cortex	Alzheimer's	E238792M84A	84	M	Excluded
18	GSM238793	Entorhinal Cortex	Alzheimer's	E238793F79A	79	F	Excluded
19	GSM238794	Entorhinal Cortex	Alzheimer's	E238794F78A	78	F	Excluded
20	GSM238795	Entorhinal Cortex	Alzheimer's	E238795F91A	91	F	Excluded
21	GSM238796	Entorhinal Cortex	Alzheimer's	E238796M86A	86	M	Excluded
22	GSM238797	Entorhinal Cortex	Alzheimer's	E238797NA0A	N/A	N/A	Excluded
23	GSM238798	Entorhinal Cortex	Alzheimer's	E238798M80A	80	M	Excluded
24	GSM119628	Hippocampus	Normal	H119628M85N	85	M	Excluded
25	GSM119629	Hippocampus	Normal	H119629M80N	80	M	Excluded
26	GSM119630	Hippocampus	Normal	H119630M80N	80	M	Excluded
27	GSM119631	Hippocampus	Normal	H119631F102N	102	F	Excluded
28	GSM119632	Hippocampus	Normal	H119632M63N	63	M	Excluded
29	GSM119633	Hippocampus	Normal	H119633M79N	79	M	Excluded
30	GSM119634	Hippocampus	Normal	H119634M76N	76	M	Excluded
31	GSM119635	Hippocampus	Normal	H119635M83N	83	M	Excluded
32	GSM119636	Hippocampus	Normal	H119636M79N	79	M	Excluded
33	GSM119637	Hippocampus	Normal	H119637F88N	88	F	Excluded
34	GSM119638	Hippocampus	Normal	H119638F73N	73	F	Excluded
35	GSM119639	Hippocampus	Normal	H119639M69N	69	M	Excluded
36	GSM119640	Hippocampus	Normal	H119640M78N	78	M	Excluded
37	GSM238799	Hippocampus	Alzheimer's	H238799F73A	73	F	Included
38	GSM238800	Hippocampus	Alzheimer's	H238800M81A	81	M	Included
39	GSM238801	Hippocampus	Alzheimer's	H238801M78A	78	M	Included
40	GSM238802	Hippocampus	Alzheimer's	H238802M75A	75	M	Included
41	GSM238803	Hippocampus	Alzheimer's	H238803F70A	70	F	Included
42	GSM238804	Hippocampus	Alzheimer's	H238804F85A	85	F	Included
43	GSM238805	Hippocampus	Alzheimer's	H238805F77A	77	F	Included
44	GSM238806	Hippocampus	Alzheimer's	H238806M79A	79	M	Included
45	GSM238807	Hippocampus	Alzheimer's	H238807M88A	88	M	Included
46	GSM238808	Hippocampus	Alzheimer's	H238808M72A	72	M	Included
47	GSM119641	Medial Temporal Gyrus	Normal	MT119641M85N	85	M	Excluded
48	GSM119642	Medial Temporal Gyrus	Normal	MT119642M80N	80	M	Excluded
49	GSM119643	Medial Temporal Gyrus	Normal	MT119643F102N	102	F	Excluded
50	GSM119644	Medial Temporal Gyrus	Normal	MT119644M63N	63	M	Excluded
51	GSM119645	Medial Temporal Gyrus	Normal	MT119645M79N	79	M	Excluded
52	GSM119646	Medial Temporal Gyrus	Normal	MT119646M83N	83	M	Excluded
53	GSM119647	Medial Temporal Gyrus	Normal	MT119647M79N	79	M	Excluded
54	GSM119648	Medial Temporal Gyrus	Normal	MT119648F88N	88	F	Excluded
55	GSM119649	Medial Temporal Gyrus	Normal	MT119649F82N	82	F	Included
56	GSM119650	Medial Temporal Gyrus	Normal	MT119650F73N	73	F	Excluded
57	GSM119651	Medial Temporal Gyrus	Normal	MT119651M69N	69	M	Excluded
58	GSM119652	Medial Temporal Gyrus	Normal	MT119652M78N	78	M	Excluded
59	GSM238809	Medial Temporal Gyrus	Alzheimer's	MT238809M81A	81	M	Excluded
60	GSM238810	Medial Temporal Gyrus	Alzheimer's	MT238810M72A	72	M	Included
61	GSM238811	Medial Temporal Gyrus	Alzheimer's	MT238811M75A	75	M	Included
62	GSM238812	Medial Temporal Gyrus	Alzheimer's	MT238812M78A	78	M	Included
63	GSM238813	Medial Temporal Gyrus	Alzheimer's	MT238813M75A	75	M	Excluded
64	GSM238815	Medial Temporal Gyrus	Alzheimer's	MT238815F95A	95	F	Included
65	GSM238816	Medial Temporal Gyrus	Alzheimer's	MT238816F81A	81	F	Included
66	GSM238817	Medial Temporal Gyrus	Alzheimer's	MT238817F85A	85	F	Included
67	GSM238818	Medial Temporal Gyrus	Alzheimer's	MT238818M79A	79	M	Included
68	GSM238819	Medial Temporal Gyrus	Alzheimer's	MT238819F82A	82	F	Included
69	GSM238820	Medial Temporal Gyrus	Alzheimer's	MT238820M88A	88	M	Included
70	GSM238821	Medial Temporal Gyrus	Alzheimer's	MT238821M72A	72	M	Included
71	GSM238822	Medial Temporal Gyrus	Alzheimer's	MT238822F73A	73	F	Excluded
72	GSM238823	Medial Temporal Gyrus	Alzheimer's	MT238823M87A	87	M	Included
73	GSM238824	Medial Temporal Gyrus	Alzheimer's	MT238824M68A	68	M	Included
74	GSM238825	Medial Temporal Gyrus	Alzheimer's	MT238825F80A	80	F	Included
75	GSM119653	Posterior Cingulate	Normal	PC119653M85N	85	M	Included
76	GSM119654	Posterior Cingulate	Normal	PC119654M80N	80	M	Included
77	GSM119655	Posterior Cingulate	Normal	PC119655F102N	102	F	Included
78	GSM119656	Posterior Cingulate	Normal	PC119656M63N	63	M	Included
79	GSM119657	Posterior Cingulate	Normal	PC119657M79N	79	M	Included
80	GSM119658	Posterior Cingulate	Normal	PC119658M76N	76	M	Included
81	GSM119659	Posterior Cingulate	Normal	PC119659M83N	83	M	Included
82	GSM119660	Posterior Cingulate	Normal	PC119660M79N	79	M	Included
83	GSM119661	Posterior Cingulate	Normal	PC119661F88N	88	F	Excluded
84	GSM119662	Posterior Cingulate	Normal	PC119662F82N	82	F	Included
85	GSM119663	Posterior Cingulate	Normal	PC119663F73N	73	F	Included
86	GSM119664	Posterior Cingulate	Normal	PC119664M69N	69	M	Included
87	GSM119665	Posterior Cingulate	Normal	PC119665M78N	78	M	Included
88	GSM238826	Posterior Cingulate	Alzheimer's	PC238826F73A	73	F	Included
89	GSM238827	Posterior Cingulate	Alzheimer's	PC238827M81A	81	M	Included
90	GSM238834	Posterior Cingulate	Alzheimer's	PC238834M78A	78	M	Included
91	GSM238835	Posterior Cingulate	Alzheimer's	PC238835M75A	75	M	Included
92	GSM238837	Posterior Cingulate	Alzheimer's	PC238837M68A	68	M	Included
93	GSM238838	Posterior Cingulate	Alzheimer's	PC238838F70A	70	F	Included
94	GSM238839	Posterior Cingulate	Alzheimer's	PC238839F85A	85	F	Included
95	GSM238840	Posterior Cingulate	Alzheimer's	PC238840M79A	79	M	Included
96	GSM238841	Posterior Cingulate	Alzheimer's	PC238841M88A	88	M	Included
97	GSM119666	Superior Frontal Gyrus	Normal	SF119666M79N	79	M	Excluded
98	GSM119667	Superior Frontal Gyrus	Normal	SF119667F88N	88	F	Included
99	GSM119668	Superior Frontal Gyrus	Normal	SF119668F82N	82	F	Included
100	GSM119669	Superior Frontal Gyrus	Normal	SF119669F73N	73	F	Excluded
101	GSM119670	Superior Frontal Gyrus	Normal	SF119670F102N	102	F	Included
102	GSM119671	Superior Frontal Gyrus	Normal	SF119671M63N	63	M	Included
103	GSM119672	Superior Frontal Gyrus	Normal	SF119672M79N	79	M	Included
104	GSM119673	Superior Frontal Gyrus	Normal	SF119673M76N	76	M	Included
105	GSM119674	Superior Frontal Gyrus	Normal	SF119674M83N	83	M	Included
106	GSM119675	Superior Frontal Gyrus	Normal	SF119675M69N	69	M	Excluded
107	GSM119676	Superior Frontal Gyrus	Normal	SF119676M78N	78	M	Excluded
108	GSM238842	Superior Frontal Gyrus	Alzheimer's	SF238842F73A	73	F	Included
109	GSM238843	Superior Frontal Gyrus	Alzheimer's	SF238843M81A	81	M	Included
110	GSM238844	Superior Frontal Gyrus	Alzheimer's	SF238844M72A	72	M	Included
111	GSM238845	Superior Frontal Gyrus	Alzheimer's	SF238845M75A	75	M	Included
112	GSM238846	Superior Frontal Gyrus	Alzheimer's	SF238846M78A	78	M	Included
113	GSM238847	Superior Frontal Gyrus	Alzheimer's	SF238847M75A	75	M	Included
114	GSM238848	Superior Frontal Gyrus	Alzheimer's	SF238848M87A	87	M	Included
115	GSM238851	Superior Frontal Gyrus	Alzheimer's	SF238851F95A	95	F	Included
116	GSM238854	Superior Frontal Gyrus	Alzheimer's	SF238854M68A	68	M	Included
117	GSM238855	Superior Frontal Gyrus	Alzheimer's	SF238855F95A	95	F	Included
118	GSM238856	Superior Frontal Gyrus	Alzheimer's	SF238856F70A	70	F	Included
119	GSM238857	Superior Frontal Gyrus	Alzheimer's	SF238857F85A	85	F	Included
120	GSM238858	Superior Frontal Gyrus	Alzheimer's	SF238858F83A	83	F	Included
121	GSM238860	Superior Frontal Gyrus	Alzheimer's	SF238860F77A	77	F	Included
122	GSM238861	Superior Frontal Gyrus	Alzheimer's	SF238861F83A	83	F	Included
123	GSM238862	Superior Frontal Gyrus	Alzheimer's	SF238862M68A	68	M	Included
124	GSM238863	Superior Frontal Gyrus	Alzheimer's	SF238863M79A	79	M	Excluded
125	GSM238864	Superior Frontal Gyrus	Alzheimer's	SF238864F82A	82	F	Included
126	GSM238865	Superior Frontal Gyrus	Alzheimer's	SF238865M88A	88	M	Included
127	GSM238867	Superior Frontal Gyrus	Alzheimer's	SF238867F80A	80	F	Included
128	GSM238868	Superior Frontal Gyrus	Alzheimer's	SF238868M74A	74	M	Excluded
129	GSM238870	Superior Frontal Gyrus	Alzheimer's	SF238870M72A	72	M	Included
130	GSM238871	Superior Frontal Gyrus	Alzheimer's	SF238871M80A	80	M	Included
131	GSM119677	Primary Visual Cortex	Normal	V119677M85N	85	M	Included
132	GSM119678	Primary Visual Cortex	Normal	V119678M80N	80	M	Included
133	GSM119679	Primary Visual Cortex	Normal	V119679M63N	63	M	Included
134	GSM119680	Primary Visual Cortex	Normal	V119680M79N	79	M	Included
135	GSM119681	Primary Visual Cortex	Normal	V119681M76N	76	M	Included
136	GSM119682	Primary Visual Cortex	Normal	V119682M83N	83	M	Included
137	GSM119683	Primary Visual Cortex	Normal	V119683M79N	79	M	Included
138	GSM119684	Primary Visual Cortex	Normal	V119684F88N	88	F	Included
139	GSM119685	Primary Visual Cortex	Normal	V119685F82N	82	F	Included
140	GSM119686	Primary Visual Cortex	Normal	V119686F73N	73	F	Included
141	GSM119687	Primary Visual Cortex	Normal	V119687M69N	69	M	Included
142	GSM119688	Primary Visual Cortex	Normal	V119688M78N	78	M	Included
143	GSM238872	Primary Visual Cortex	Alzheimer's	V238872F73A	73	F	Included
144	GSM238873	Primary Visual Cortex	Alzheimer's	V238873M81A	81	M	Included
145	GSM238874	Primary Visual Cortex	Alzheimer's	V238874M75A	75	M	Included
146	GSM238875	Primary Visual Cortex	Alzheimer's	V238875M78A	78	M	Included
147	GSM238877	Primary Visual Cortex	Alzheimer's	V238877M75A	75	M	Excluded
148	GSM238941	Primary Visual Cortex	Alzheimer's	V238941M87A	87	M	Excluded
149	GSM238942	Primary Visual Cortex	Alzheimer's	V238942F95A	95	F	Included
150	GSM238943	Primary Visual Cortex	Alzheimer's	V238943M68A	68	M	Excluded
151	GSM238944	Primary Visual Cortex	Alzheimer's	V238944F70A	70	F	Included
152	GSM238945	Primary Visual Cortex	Alzheimer's	V238945F81A	81	F	Excluded
153	GSM238946	Primary Visual Cortex	Alzheimer's	V238946F85A	85	F	Included
154	GSM238947	Primary Visual Cortex	Alzheimer's	V238947M68A	68	M	Included
155	GSM238948	Primary Visual Cortex	Alzheimer's	V238948M79A	79	M	Included
156	GSM238949	Primary Visual Cortex	Alzheimer's	V238949F82A	82	F	Included
157	GSM238951	Primary Visual Cortex	Alzheimer's	V238951M88A	88	M	Included
158	GSM238952	Primary Visual Cortex	Alzheimer's	V238952M74A	74	M	Included
159	GSM238953	Primary Visual Cortex	Alzheimer's	V238953M72A	72	M	Included
160	GSM238955	Primary Visual Cortex	Alzheimer's	V238955M68A	68	M	Included
161	GSM238963	Primary Visual Cortex	Alzheimer's	V238963F80A	80	F	Included

Web Link:

http://arrayconsortium.tgen.org/np2/viewProject.do?action=viewProject&projectId=433773

Citations:

Liang WS, Dunckley T, Beach TG, Grover A et al. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain. Physiol Genomics 2007 Feb 12;28(3):311-22. PMID: 17077275
Liang WS, Reiman EM, Valla J, Dunckley T et al. Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 2008 Mar 18;105(11):4441-6. PMID: 18332434